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1.
Tohoku J Exp Med ; 255(1): 61-69, 2021 09.
Article in English | MEDLINE | ID: covidwho-1496649

ABSTRACT

North Italy emerged as an epicenter of COVID-19 in the Western world. The majority of studies of patients with COVID-19 have focused on hospitalized patients, and data on early outpatient treatment are limited. This research retrospectively examines consecutive symptomatic adults who did not present to a hospital but who experience laboratory confirmed (nasopharyngeal swabs) or probable COVID-19 infection. From March 12 to April 12, 2020, 124 consecutive patients with laboratory-confirmed COVID-19 infection (84%) or with epidemiologically linked exposure to a person with confirmed infection (16%) were managed at home. The diagnosis of pneumonia was made with a portable ultrasound. COVID-19 treatment was based on low-dose hydroxychloroquine with or without darunavir/cobicistat or azithromycin and enoxaparine for bedridden patients. The patients were monitored by telemedicine. The primary endpoints were clinical improvement or hospitalization, and the secondary endpoints were mortality at day 30 and at day 60. Forty-seven (37.9%) patients had mild COVID-19 infection, 44 (35.5%) had moderate COVID-19 infection, and 33 (26.6%) had severe COVID-19 infection. Four patients (3.2%) were hospitalized and there were no deaths at day 30 and at day 60. Only mild side effects were reported. Early home treatment of COVID-19 patients resulted in a low hospitalization rate with no deaths, with the limitations of the small sample size and that it was conducted within a single geographic area. We believe that this model may be easily reproduced in both cities and rural areas around the world to treat COVID-19 infection.


Subject(s)
COVID-19/epidemiology , Disease Outbreaks , SARS-CoV-2 , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19 Testing , Cobicistat/therapeutic use , Darunavir/therapeutic use , Drug Combinations , Female , Home Care Services , Hospitalization , Humans , Hydroxychloroquine/therapeutic use , Italy/epidemiology , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Telemedicine , Young Adult
3.
J Med Virol ; 93(9): 5432-5437, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1363681

ABSTRACT

This case series describes three patients affected by severe acute respiratory syndrome coronavirus 2, who developed polyradiculoneuritis as a probable neurological complication of coronavirus disease 2019 (COVID-19). A diagnosis of Guillain Barré syndrome was made on the basis of clinical symptoms, cerebrospinal fluid analysis, and electroneurography. In all of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 gr/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases, a significant decrease in amplitude of compound motor action potential cMAP. Due to the potential role of inflammation on symptoms development and prognosis, interleukin-6 (IL-6) and IL-8 levels were measured in serum and cerebrospinal fluid during the acute phase, while only serum was tested after recovery. Both IL-6 and IL-8 were found increased during the acute phase, both in the serum and cerebrospinal fluid, whereas 4 months after admission (at complete recovery), only IL-8 remained elevated in the serum. These results confirm the inflammatory response that might be linked to peripheral nervous system complications and encourage the use of IL-6 and IL-8 as prognostic biomarkers in COVID-19.


Subject(s)
COVID-19/complications , Guillain-Barre Syndrome/complications , Interleukin-6/cerebrospinal fluid , Interleukin-8/cerebrospinal fluid , Respiratory Insufficiency/complications , SARS-CoV-2/pathogenicity , Action Potentials/drug effects , Acute Disease , Aged , Anti-Bacterial Agents/therapeutic use , Biomarkers/blood , Biomarkers/cerebrospinal fluid , COVID-19/cerebrospinal fluid , COVID-19/drug therapy , COVID-19/virology , Convalescence , Darunavir/therapeutic use , Drug Combinations , Guillain-Barre Syndrome/cerebrospinal fluid , Guillain-Barre Syndrome/drug therapy , Guillain-Barre Syndrome/virology , Humans , Hydroxychloroquine/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Interleukin-6/blood , Interleukin-8/blood , Lopinavir/therapeutic use , Male , Neural Conduction/drug effects , Peripheral Nervous System/drug effects , Peripheral Nervous System/pathology , Peripheral Nervous System/virology , Prognosis , Respiratory Insufficiency/cerebrospinal fluid , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/virology , Ritonavir/therapeutic use , SARS-CoV-2/drug effects
4.
J Microbiol Immunol Infect ; 54(5): 767-775, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1284232

ABSTRACT

Despite aggressive efforts on containment measures for the coronavirus disease 2019 (COVID-19) pandemic around the world, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously spreading. Therefore, there is an urgent need for an effective antiviral agent. To date, considerable research has been conducted to develop different approaches to COVID-19 therapy. In addition to early observational studies, which could be limited by study design, small sample size, non-randomized design, or different timings of treatment, an increasing number of randomized controlled trials (RCTs) investigating the clinical efficacy and safety of antiviral agents are being carried out. This study reviews the updated findings of RCTs regarding the clinical efficacy of eight antiviral agents against COVID-19, including remdesivir, lopinavir/ritonavir, favipiravir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir, baloxavir, umifenovir, darunavir/cobicistat, and their combinations. Treatment with remdesivir could accelerate clinical improvement; however, it lacked additional survival benefits. Moreover, 5-day regimen of remdesivir might show adequate effectiveness in patients with mild to moderate COVID-19. Favipiravir was only marginally effective regarding clinical improvement and virological assessment based on the results of small RCTs. The present evidence suggests that sofosbuvir/daclatasvir may improve survival and clinical outcomes in patients with COVID-19. However, the sample sizes for analysis were relatively small, and all studies were exclusively conducted in Iran. Further larger RCTs in other countries are warranted to support these findings. In contrast, the present findings of limited RCTs did not indicate the use of lopinavir/ritonavir, sofosbuvir/ledipasvir, baloxavir, umifenovir, and darunavir/cobicistat in the treatment of patients hospitalized for COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Amides/therapeutic use , Carbamates/therapeutic use , Cobicistat/therapeutic use , Darunavir/therapeutic use , Dibenzothiepins/therapeutic use , Drug Combinations , Drug Therapy, Combination , Humans , Imidazoles/therapeutic use , Indoles/therapeutic use , Iran , Lopinavir/therapeutic use , Morpholines/therapeutic use , Pyrazines/therapeutic use , Pyridones/therapeutic use , Pyrrolidines/therapeutic use , Randomized Controlled Trials as Topic , Ritonavir/therapeutic use , SARS-CoV-2 , Sofosbuvir/therapeutic use , Treatment Outcome , Triazines/therapeutic use , Valine/analogs & derivatives , Valine/therapeutic use
5.
J Med Virol ; 93(9): 5432-5437, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1258081

ABSTRACT

This case series describes three patients affected by severe acute respiratory syndrome coronavirus 2, who developed polyradiculoneuritis as a probable neurological complication of coronavirus disease 2019 (COVID-19). A diagnosis of Guillain Barré syndrome was made on the basis of clinical symptoms, cerebrospinal fluid analysis, and electroneurography. In all of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 gr/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases, a significant decrease in amplitude of compound motor action potential cMAP. Due to the potential role of inflammation on symptoms development and prognosis, interleukin-6 (IL-6) and IL-8 levels were measured in serum and cerebrospinal fluid during the acute phase, while only serum was tested after recovery. Both IL-6 and IL-8 were found increased during the acute phase, both in the serum and cerebrospinal fluid, whereas 4 months after admission (at complete recovery), only IL-8 remained elevated in the serum. These results confirm the inflammatory response that might be linked to peripheral nervous system complications and encourage the use of IL-6 and IL-8 as prognostic biomarkers in COVID-19.


Subject(s)
COVID-19/complications , Guillain-Barre Syndrome/complications , Interleukin-6/cerebrospinal fluid , Interleukin-8/cerebrospinal fluid , Respiratory Insufficiency/complications , SARS-CoV-2/pathogenicity , Action Potentials/drug effects , Acute Disease , Aged , Anti-Bacterial Agents/therapeutic use , Biomarkers/blood , Biomarkers/cerebrospinal fluid , COVID-19/cerebrospinal fluid , COVID-19/drug therapy , COVID-19/virology , Convalescence , Darunavir/therapeutic use , Drug Combinations , Guillain-Barre Syndrome/cerebrospinal fluid , Guillain-Barre Syndrome/drug therapy , Guillain-Barre Syndrome/virology , Humans , Hydroxychloroquine/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Interleukin-6/blood , Interleukin-8/blood , Lopinavir/therapeutic use , Male , Neural Conduction/drug effects , Peripheral Nervous System/drug effects , Peripheral Nervous System/pathology , Peripheral Nervous System/virology , Prognosis , Respiratory Insufficiency/cerebrospinal fluid , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/virology , Ritonavir/therapeutic use , SARS-CoV-2/drug effects
6.
AIDS Res Hum Retroviruses ; 37(4): 283-291, 2021 04.
Article in English | MEDLINE | ID: covidwho-1207222

ABSTRACT

The aim of this study was to evaluate both positive outcomes, including reduction of respiratory support aid and duration of hospital stay, and negative ones, including mortality and a composite of invasive mechanical ventilation or death, in patients with coronavirus disease 2019 (COVID-19) pneumonia treated with or without oral darunavir/cobicistat (DRV/c, 800/150 mg/day) used in different treatment durations. The secondary objective was to evaluate the percentage of patients treated with DRV/c who were exposed to potentially severe drug-drug interactions (DDIs) and died during hospitalization. This observational retrospective study was conducted in consecutive patients with COVID-19 pneumonia admitted to a tertiary care hospital in Modena, Italy. Kaplan-Meier survival curves and Cox proportional hazards regression were used to compare patients receiving standard of care with or without DRV/c. Adjustment for key confounders was applied. Two hundred seventy-three patients (115 on DRV/c) were included, 75.8% males, mean age was 64.6 (±13.2) years. Clinical improvement was similar between the groups, depicted by respiratory aid switch (p > .05). The same was observed for duration of hospital stay [13.2 (±8.9) for DRV/c vs. 13.4 (±7.2) days for no-DRV/c, p = .9]. Patients on DRV/c had higher rates of mortality (25.2% vs. 10.1%, p < .0001. The rate of composite outcome of mechanical ventilation and death was higher in the DRV/c group (37.4% vs. 25.3%, p = .03). Multiple serious DDI associated with DRV/c were observed in the 19 patients who died. DRV/c should not be recommended as a treatment option for COVID-19 pneumonia outside clinical trials.


Subject(s)
Anti-HIV Agents/therapeutic use , COVID-19/drug therapy , Cobicistat/therapeutic use , Darunavir/therapeutic use , Adult , Anti-HIV Agents/adverse effects , COVID-19/mortality , COVID-19/virology , Cobicistat/adverse effects , Darunavir/adverse effects , Drug Combinations , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/isolation & purification
7.
BMC Infect Dis ; 21(1): 382, 2021 Apr 26.
Article in English | MEDLINE | ID: covidwho-1204046

ABSTRACT

BACKGROUND: The epidemiology and outcomes of COVID-19 patients in Thailand are scarce. METHODS: This retrospective cohort study included adult hospitalized patients who were diagnosed with COVID-19 at Siriraj Hospital during February 2020 to April 2020. RESULTS: The prevalence of COVID-19 was 7.5% (107 COVID-19 patients) among 1409 patients who underwent RT-PCR for SARS-CoV-2 detection at our hospital during the outbreak period. Patients with COVID-19 presented with symptoms in 94.4%. Among the 104 patients who were treated with antiviral medications, 78 (75%) received 2-drug regimen (lopinavir/ritonavir or darunavir/ritonavir plus chloroquine or hydroxychloroquine), and 26 (25%) received a 3-drug regimen with favipiravir added to the 2-drug regimen. Disease progression was observed in 18 patients (16.8%). All patients with COVID-19 were discharged alive. CONCLUSIONS: The prevalence of COVID-19 was 7.5% among patients who underwent RT-PCR testing, and 10% among those having risk factors for COVID-19 acquisition. Combination antiviral therapies for COVID-19 patients were well-tolerated and produced a favorable outcome.


Subject(s)
COVID-19/epidemiology , Adult , Aged , Aged, 80 and over , Amides/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Chloroquine/therapeutic use , Darunavir/therapeutic use , Disease Progression , Drug Combinations , Female , Hospitals , Hospitals, University , Humans , Hydroxychloroquine/therapeutic use , Lopinavir/therapeutic use , Male , Middle Aged , Pyrazines/therapeutic use , Referral and Consultation , Retrospective Studies , Ritonavir/therapeutic use , Thailand/epidemiology , Treatment Outcome , Young Adult
8.
AIDS Res Hum Retroviruses ; 37(4): 283-291, 2021 04.
Article in English | MEDLINE | ID: covidwho-1096474

ABSTRACT

The aim of this study was to evaluate both positive outcomes, including reduction of respiratory support aid and duration of hospital stay, and negative ones, including mortality and a composite of invasive mechanical ventilation or death, in patients with coronavirus disease 2019 (COVID-19) pneumonia treated with or without oral darunavir/cobicistat (DRV/c, 800/150 mg/day) used in different treatment durations. The secondary objective was to evaluate the percentage of patients treated with DRV/c who were exposed to potentially severe drug-drug interactions (DDIs) and died during hospitalization. This observational retrospective study was conducted in consecutive patients with COVID-19 pneumonia admitted to a tertiary care hospital in Modena, Italy. Kaplan-Meier survival curves and Cox proportional hazards regression were used to compare patients receiving standard of care with or without DRV/c. Adjustment for key confounders was applied. Two hundred seventy-three patients (115 on DRV/c) were included, 75.8% males, mean age was 64.6 (±13.2) years. Clinical improvement was similar between the groups, depicted by respiratory aid switch (p > .05). The same was observed for duration of hospital stay [13.2 (±8.9) for DRV/c vs. 13.4 (±7.2) days for no-DRV/c, p = .9]. Patients on DRV/c had higher rates of mortality (25.2% vs. 10.1%, p < .0001. The rate of composite outcome of mechanical ventilation and death was higher in the DRV/c group (37.4% vs. 25.3%, p = .03). Multiple serious DDI associated with DRV/c were observed in the 19 patients who died. DRV/c should not be recommended as a treatment option for COVID-19 pneumonia outside clinical trials.


Subject(s)
Anti-HIV Agents/therapeutic use , COVID-19/drug therapy , Cobicistat/therapeutic use , Darunavir/therapeutic use , Adult , Anti-HIV Agents/adverse effects , COVID-19/mortality , COVID-19/virology , Cobicistat/adverse effects , Darunavir/adverse effects , Drug Combinations , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/isolation & purification
9.
J Antimicrob Chemother ; 76(2): 482-486, 2021 01 19.
Article in English | MEDLINE | ID: covidwho-939573

ABSTRACT

BACKGROUND: Combination therapy with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir has been suggested as an approach to improve the outcome of patients with moderate/severe COVID-19 infection. OBJECTIVES: To examine the safety of combination therapy with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir. METHODS: This was an observational cohort study of patients hospitalized for COVID-19 pneumonia treated with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir. Clinical evaluations, electrocardiograms and the pharmacokinetics of hydroxychloroquine, darunavir and lopinavir were examined according to clinical practice and guidelines. RESULTS: Twenty-one patients received hydroxychloroquine with lopinavir/ritonavir (median age 68 years; 10 males) and 25 received hydroxychloroquine with darunavir/ritonavir (median age 71 years; 15 males). During treatment, eight patients (17.4%) developed ECG abnormalities. Ten patients discontinued treatment, including seven for ECG abnormalities a median of 5 (range 2-6) days after starting treatment. All ECG abnormalities reversed 1-2 days after interrupting treatment. Four patients died within 14 days. ECG abnormalities were significantly associated with age over 70 years, coexisting conditions (such as hypertension, chronic cardiovascular disease and kidney failure) and initial potential drug interactions, but not with the hydroxychloroquine concentration. CONCLUSIONS: Of the patients with COVID-19 who received hydroxychloroquine with lopinavir or darunavir, 17% had ECG abnormalities, mainly related to age or in those with a history of cardiovascular disease.


Subject(s)
Antiviral Agents/adverse effects , COVID-19/drug therapy , Darunavir/adverse effects , Hydroxychloroquine/adverse effects , Lopinavir/adverse effects , Antiviral Agents/administration & dosage , Antiviral Agents/blood , Antiviral Agents/therapeutic use , COVID-19/epidemiology , Cohort Studies , Darunavir/administration & dosage , Darunavir/blood , Darunavir/therapeutic use , Drug Therapy, Combination , Electrocardiography , France , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/blood , Hydroxychloroquine/therapeutic use , Long QT Syndrome/chemically induced , Long QT Syndrome/epidemiology , Lopinavir/administration & dosage , Lopinavir/blood , Lopinavir/therapeutic use , SARS-CoV-2 , Severity of Illness Index , Treatment Outcome
10.
Medicina (Kaunas) ; 56(11)2020 Oct 29.
Article in English | MEDLINE | ID: covidwho-902595

ABSTRACT

BACKGROUND AND OBJECTIVES: Streptococcus pneumoniae urinary antigen (u-Ag) testing has recently gained attention in the early diagnosis of severe and critical acute respiratory syndrome coronavirus-2/pneumococcal co-infection. The aim of this study is to assess the effectiveness of Streptococcus pneumoniae u-Ag testing in coronavirus disease 2019 (COVID-19) patients, in order to assess whether pneumococcal co-infection is associated with different mortality rate and hospital stay in these patients. MATERIALS AND METHODS: Charts, protocols, mortality, and hospitalization data of a consecutive series of COVID-19 patients admitted to a tertiary hospital in northern Italy during COVID-19 outbreak were retrospectively reviewed. All patients underwent Streptococcus pneumoniae u-Ag testing to detect an underlying pneumococcal co-infection. Covid19+/u-Ag+ and Covid19+/u-Ag- patients were compared in terms of overall survival and length of hospital stay using chi-square test and survival analysis. RESULTS: Out of 575 patients with documented pneumonia, 13% screened positive for the u-Ag test. All u-Ag+ patients underwent treatment with Ceftriaxone and Azithromycin or Levofloxacin. Lopinavir/Ritonavir or Darunavir/Cobicistat were added in 44 patients, and hydroxychloroquine and low-molecular-weight heparin (LMWH) in 47 and 33 patients, respectively. All u-Ag+ patients were hospitalized. Mortality was 15.4% and 25.9% in u-Ag+ and u-Ag- patients, respectively (p = 0.09). Survival analysis showed a better prognosis, albeit not significant, in u-Ag+ patients. Median hospital stay did not differ among groups (10 vs. 9 days, p = 0.71). CONCLUSIONS: The routine use of Streptococcus pneumoniae u-Ag testing helped to better target antibiotic therapy with a final trend of reduction in mortality of u-Ag+ COVID-19 patients having a concomitant pneumococcal infection. Randomized trials on larger cohorts are necessary in order to draw definitive conclusion.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , Coinfection/diagnosis , Coronavirus Infections/drug therapy , Hospital Mortality , Pneumonia, Pneumococcal/drug therapy , Pneumonia, Viral/drug therapy , Adult , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , Antigens, Bacterial/urine , Azithromycin/therapeutic use , Betacoronavirus , COVID-19 , Ceftriaxone/therapeutic use , Cobicistat/therapeutic use , Coinfection/urine , Coronavirus Infections/complications , Cross-Sectional Studies , Darunavir/therapeutic use , Drug Combinations , Female , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Length of Stay/statistics & numerical data , Levofloxacin/therapeutic use , Lopinavir/therapeutic use , Male , Mass Screening , Middle Aged , Pandemics , Pneumonia, Pneumococcal/complications , Pneumonia, Pneumococcal/diagnosis , Pneumonia, Pneumococcal/urine , Pneumonia, Viral/complications , Retrospective Studies , Ritonavir/therapeutic use , SARS-CoV-2 , Streptococcus pneumoniae/immunology
11.
Intern Emerg Med ; 15(8): 1389-1398, 2020 11.
Article in English | MEDLINE | ID: covidwho-805950

ABSTRACT

To date the severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), known as COVID-19, is for clinicians the most difficult global therapeutic problem. In this landscape, the management of patients with chronic kidney disease, acute kidney injury or patients undergoing immunosuppressant therapies for kidney transplant or glomerular diseases, represent a clinical challenge for nephrologists, especially in patients with severe acute lung involvement. Therefore in this setting, due to the lack of anti-COVID treatment schedules, tailored management is mandatory to reduce the side effects, as consequence of impaired renal function and drugs interactions. We report the main treatment actually used against SARS-CoV-2, underlining its possible use in the nephropatic patients and the central role of nephrologists to improve the clinical outcome.


Subject(s)
Coronavirus Infections/complications , Pneumonia, Viral/complications , Renal Insufficiency, Chronic/drug therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Amides/therapeutic use , Antibodies, Monoclonal/therapeutic use , COVID-19 , Cobicistat/therapeutic use , Coronavirus Infections/drug therapy , Darunavir/therapeutic use , Drug Combinations , Humans , Kidney/drug effects , Kidney/injuries , Kidney/physiopathology , Lopinavir/therapeutic use , Pandemics , Pneumonia, Viral/drug therapy , Pyrazines/therapeutic use , Renal Insufficiency, Chronic/complications , Renal Replacement Therapy/methods , Ritonavir/therapeutic use
12.
Yonsei Med J ; 61(9): 826-830, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-745127

ABSTRACT

We retrospectively reviewed patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections who were admitted to an intensive care unit in Daegu, South Korea. The outcomes of patients who did (cases) or did not (controls) receive darunavir-cobicistat (800-150 mg) therapy were compared. Fourteen patients received darunavir-cobicistat treatment, and 96 received other antiviral therapy (controls). Overall, the darunavir-cobicistat group comprised patients with milder illness, and the crude mortality rate of all patients in the darunavir-cobicistat group was lower than that in the controls [odds ratio (OR) 0.20, 95% confidence interval (CI) 0.04-0.89, p=0.035]. After 1:2 propensity-score matching, there were 14 patients in the darunavir-cobicistat group, and 28 patients in the controls. In propensity score-matched analysis, the darunavir-cobicistat group had lower mortality than the controls (OR 0.07, 95% CI 0.01-0.52, p=0.009). In conclusion, darunavir-cobicistat therapy was found to be associated with a significant survival benefit in critically ill patients with SARS-CoV-2 infection.


Subject(s)
Anti-HIV Agents/therapeutic use , Cobicistat/therapeutic use , Coronavirus Infections/drug therapy , Darunavir/therapeutic use , HIV Protease Inhibitors/therapeutic use , Pneumonia, Viral/drug therapy , Adult , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/adverse effects , Betacoronavirus , COVID-19 , Case-Control Studies , Cobicistat/administration & dosage , Cobicistat/adverse effects , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Critical Illness , Darunavir/administration & dosage , Darunavir/adverse effects , Female , HIV Protease Inhibitors/administration & dosage , HIV Protease Inhibitors/adverse effects , Humans , Intensive Care Units , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Republic of Korea/epidemiology , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Treatment Outcome
13.
Ann Ital Chir ; 91: 273-276, 2020.
Article in English | MEDLINE | ID: covidwho-739593

ABSTRACT

CASE REPORT: A 64-year-old woman presented to our emergency department during the outbreak of the covid-19 emergency in Italy with syncope, anosmia, mild dyspnoea and atypical chest and dorsal pain. A chest CT scan showed an acute type B aortic dissection (ATBAD) and bilateral lung involvement with ground-glass opacity, compatible with interstitial pneumonia. Nasopharyngeal swabs resulted positive for SARS-CoV-2. For the persistence of chest pain, despite the analgesic therapy, we decided to treat her with a TEVAR. Patient's chest and back pain resolved during the first few days after the procedure. No surgical or respiratory complications occurred and the patient was discharged 14 days after surgery. DISCUSSION: By performing the operation under local anesthesia, it was possible to limit both the staff inside the operatory room and droplet/aerosol release. Since we had to perform the operation in a hemodynamics room, thanks to the limited extension of the endoprosthesis and the good caliber of the right vertebral artery we were able to reduce the risk of spinal cord ischemia despite the lack of a revascularization of the left subclavian artery. CONCLUSIONS: A minimally invasive total endovascular approach allows, through local anesthesia and percutaneous access, to avoid surgical cut down and orotracheal intubation. This, combined with a defined management protocol for infected patients, seems to be a reasonable way to perform endovascular aortic procedures in urgent setting, even in a SARSCoV- 2 positive patient. KEY WORDS: COVID-19, Dissection, TEVAR.


Subject(s)
Aneurysm, Dissecting/surgery , Aortic Aneurysm, Thoracic/surgery , Betacoronavirus/isolation & purification , Blood Vessel Prosthesis Implantation/methods , Coronavirus Infections/prevention & control , Endovascular Procedures/methods , Infection Control/methods , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Anesthesia, Local , Aneurysm, Dissecting/complications , Antibiotic Prophylaxis , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , Aortic Aneurysm, Thoracic/complications , COVID-19 , Contraindications, Procedure , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Coronavirus Infections/transmission , Darunavir/therapeutic use , Diabetes Mellitus, Type 2/complications , Drug Therapy, Combination , Enoxaparin/therapeutic use , Female , Humans , Hydroxychloroquine/therapeutic use , Intraoperative Complications/prevention & control , Intubation, Intratracheal/adverse effects , Middle Aged , Nasopharynx/virology , Operating Rooms , Patient Isolation , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pneumonia, Viral/transmission , Ritonavir/therapeutic use , SARS-CoV-2 , Spinal Cord Ischemia/prevention & control , Vertebral Artery/surgery
14.
Clin Pharmacokinet ; 59(10): 1251-1260, 2020 10.
Article in English | MEDLINE | ID: covidwho-734040

ABSTRACT

BACKGROUND: Darunavir is an anti-HIV protease inhibitor repurposed for SARS-CoV-2 treatment. OBJECTIVE: The aim of this study was to assess the population pharmacokinetics of darunavir in SARS-CoV-2 patients compared with HIV patients. METHODS: Two separate models were created by means of a nonlinear mixed-effect approach. The influence of clinical covariates on each basic model was tested and the association of significant covariates with darunavir parameters was assessed at multivariate regression and classification and regression tree (CART) analyses. Monte Carlo simulation assessed the influence of covariates on the darunavir concentration versus time profile. RESULTS: A one-compartment model well-described darunavir concentrations in both groups. In SARS-CoV-2 patients (n = 30), interleukin (IL)-6 and body surface area were covariates associated with darunavir oral clearance (CL/F) and volume of distribution (Vd), respectively; no covariates were identified in HIV patients (n = 25). Darunavir CL/F was significantly lower in SARS-CoV-2 patients compared with HIV patients (4.1 vs. 10.3 L/h; p < 0.001). CART analysis found that an IL-6 level of 18 pg/mL may split the SARS-CoV-2 population in patients with low versus high darunavir CL/F (mean ± standard deviation 3.47 ± 1.90 vs. 8.03 ± 3.24 L/h; proportion of reduction in error = 0.46). Median (interquartile range) darunavir CL/F was significantly lower in SARS-CoV-2 patients with IL-6 levels ≥ 18 pg/mL than in SARS-CoV-2 patients with IL-6 levels < 18 pg/mL or HIV patients (2.78 [2.16-4.47] vs. 7.24 [5.88-10.38] vs. 9.75 [8.45-13.79] L/h, respectively; p < 0.0001). Increasing IL-6 levels affected darunavir concentration versus time simulated profiles. We hypothesized that increases in IL-6 levels associated with severe SARS-CoV-2 disease may downregulate the cytochrome P450 (CYP) 3A4-mediated metabolism of darunavir. CONCLUSIONS: This is a proof-of-concept of SARS-CoV-2 disease-drug interactions, and may support the need for optimal dose selection of sensitive CYP3A4 substrates in severe SARS-CoV-2 patients.


Subject(s)
Coronavirus Infections/drug therapy , Darunavir/pharmacokinetics , HIV Infections/drug therapy , HIV Protease Inhibitors/pharmacokinetics , Interleukin-6/blood , Pneumonia, Viral/drug therapy , Adult , Age Factors , Aged , Betacoronavirus , Body Weights and Measures , COVID-19 , Comorbidity , Cytochrome P-450 CYP3A , Darunavir/therapeutic use , Dose-Response Relationship, Drug , Female , HIV Protease Inhibitors/therapeutic use , Humans , Male , Metabolic Clearance Rate , Middle Aged , Models, Biological , Monte Carlo Method , Pandemics , Retrospective Studies , SARS-CoV-2 , Sex Factors
15.
PLoS One ; 15(8): e0237831, 2020.
Article in English | MEDLINE | ID: covidwho-725099

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) can lead to respiratory failure due to severe immune response. Treatment targeting this immune response might be beneficial but there is limited evidence on its efficacy. The aim of this study was to determine if early treatment of patients with COVID-19 pneumonia with tocilizumab and/or steroids was associated with better outcome. METHODS: This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. SOC consisted of hydroxychloroquine 400mg bid plus, in those admitted before March 24th, also darunavir/ritonavir. Anti-inflammatory treatment consisted of either tocilizumab (8mg/kg intravenously or 162mg subcutaneously) or methylprednisolone 1 mg/kg for 5 days or both. Failure was defined as intubation or death, and the endpoints were failure-free survival (primary endpoint) and overall survival (secondary) at day 30. Difference between the groups was estimated as Hazard Ratio by a propensity score weighted Cox regression analysis (HROW). RESULTS: Overall, 196 adults were included in the analyses. They were mainly male (67.4%), with comorbidities (78.1%) and severe COVID-19 pneumonia (83.7%). Median age was 67.9 years (range, 30-100) and median PaO2/FiO2 200 mmHg (IQR 133-289). Among them, 130 received early anti-inflammatory treatment with: tocilizumab (n = 29, 22.3%), methylprednisolone (n = 45, 34.6%), or both (n = 56, 43.1%). The adjusted failure-free survival among tocilizumab/methylprednisolone/SOC treated patients vs. SOC was 80.8% (95%CI, 72.8-86.7) vs. 64.1% (95%CI, 51.3-74.0), HROW 0.48, 95%CI, 0.23-0.99; p = 0.049. The overall survival among tocilizumab/methylprednisolone/SOC patients vs. SOC was 85.9% (95%CI, 80.7-92.6) vs. 71.9% (95%CI, 46-73), HROW 0.41, 95%CI: 0.19-0.89, p = 0.025. CONCLUSION: Early adjunctive treatment with tocilizumab, methylprednisolone or both may improve outcomes in non-intubated patients with COVID-19 pneumonia.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Coronavirus Infections/drug therapy , Methylprednisolone/therapeutic use , Pneumonia, Viral/drug therapy , Adult , Aged , Aged, 80 and over , Anti-Inflammatory Agents/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Antimalarials/administration & dosage , Antimalarials/therapeutic use , Betacoronavirus , COVID-19 , Coronavirus Infections/virology , Darunavir/therapeutic use , Female , Follow-Up Studies , HIV Protease Inhibitors/therapeutic use , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/therapeutic use , Male , Methylprednisolone/administration & dosage , Middle Aged , Pandemics , Pneumonia, Viral/virology , Ritonavir/therapeutic use , SARS-CoV-2 , Treatment Outcome
16.
J Affect Disord ; 277: 337-340, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-722855

ABSTRACT

BACKGROUND: In December 2019, the novel coronavirus (SARS-CoV-2) infection was first reported in Wuhan city, central China, which has spread rapidly. The common clinical features of patients with SARS-CoV-2 infection included fever, fatigue, and damage to the respiratory or digestive system. However, it is still unclear whether SARS-CoV-2 infection could cause damage to the central nervous system (CNS) inducing psychiatric symptoms. CASE REPORT: Herein, we present the first case of SARS-CoV-2 infection with manic-like symptoms and describe the diagnosis, clinical course, and treatment of the case, focusing on the identifications of SARS-CoV-2 in the specimen of cerebrospinal fluid (CSF). The patient developed manic-like symptoms when his vital signs recovered on illness day 17. After manic-like attack, the detection of SARS-CoV-2 specific IgG antibody in CSF was positive, while the reverse transcriptase-polymerase chain reaction (RT-PCR) on CSF for the SARS-CoV-2 was negative. The patient received Olanzapine for treatment and his mood problems concurrently improved as indicated by scores of Young Manic Rating Scale (YMRS). LIMITATION: This is a single case report only, and the RT-PCR test for SARS-CoV-2 in CSF was not performed simultaneously when SARS-CoV-2 was positive in samples of sputum and stool. CONCLUSION: This first case of COVID-19 patient with manic-like symptoms highlights the importance of evaluation of mental health status and may contribute to our understanding of potential risk of CNS impairments by SARS-CoV-2 infection.


Subject(s)
Bipolar Disorder/etiology , Coronavirus Infections/complications , Pneumonia, Viral/complications , Antibodies, Viral/cerebrospinal fluid , Antipsychotic Agents/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus , Bipolar Disorder/cerebrospinal fluid , Bipolar Disorder/diagnosis , Bipolar Disorder/drug therapy , Brain/diagnostic imaging , COVID-19 , COVID-19 Testing , Chest Pain , China , Clinical Laboratory Techniques , Cobicistat/therapeutic use , Coronavirus Infections/cerebrospinal fluid , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Darunavir/therapeutic use , Dyspnea , Fever , Glucocorticoids/therapeutic use , Humans , Indoles/therapeutic use , Magnetic Resonance Imaging , Male , Methylprednisolone/therapeutic use , Middle Aged , Moxifloxacin/therapeutic use , Olanzapine/therapeutic use , Pandemics , Pharyngitis , Pneumonia, Viral/cerebrospinal fluid , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2
18.
Heart Vessels ; 36(1): 115-120, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-649079

ABSTRACT

INTRODUCTION: Most of the drugs associations that have been used to treat patients with SARS-CoV-2 infection increase the risk of prolongation of the corrected QT interval (QTc). OBJECTIVE: To evaluate the effects of an association therapy of hydroxychloroquine (HY) plus ritonavir/darunavir (RD) or azithromycin (AZ) on QTc intervals. METHODS: At the beginning of COVID-19 pandemic patients admitted to our hospital were treated with the empiric association of HY/RD; one week later the therapeutic protocol was modified with the combination of HY/AZ. Patients underwent an ECG at baseline, then 3 and 7 days after starting therapy. We prospectively enrolled 113 patients (61 in the HY/RD group-52 in the HY/AZ group). RESULTS: A significant increase in median QTc was reported after seven days of therapy in both groups: from 438 to 452 ms in HY/RD patients; from 433 to 440 ms in HY/AZ patients (p = 0.001 for both). 23 patients (21.2%) had a QTc > 500 ms at 7 days. The risk of developing a QTc > 500 ms was greater in patients with prolonged baseline QTc values (≥ 440 ms for female and ≥ 460 ms for male patients) (OR 7.10 (95% IC 1.88-26.81); p = 0.004) and in patients with an increase in the QTc > 40 ms 3 days after onset of treatment (OR 30.15 (95% IC 6.96-130.55); p = 0.001). One patient per group suffered a malignant ventricular arrhythmia. CONCLUSION: Hydroxychloroquine with both ritonavir/darunavir or azithromycin therapy significantly increased the QTc-interval at 7 days. The risk of developing malignant arrhythmias remained relatively low when these drugs were administered for a limited period of time.


Subject(s)
Azithromycin/adverse effects , COVID-19/drug therapy , Darunavir/adverse effects , Electrocardiography/drug effects , Hydroxychloroquine/therapeutic use , Long QT Syndrome/chemically induced , Ritonavir/adverse effects , Aged , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/epidemiology , Darunavir/therapeutic use , Enzyme Inhibitors/therapeutic use , Female , Humans , Long QT Syndrome/physiopathology , Male , Middle Aged , Ritonavir/therapeutic use , SARS-CoV-2
19.
J Popul Ther Clin Pharmacol ; 27(S Pt 1): e26-e30, 2020 Jul 03.
Article in English | MEDLINE | ID: covidwho-638865

ABSTRACT

At the end of December 2019, the Health Commission of the city of Wuhan, China, alerted the World Health Organization (WHO) to a pneumonia cluster in the city. The cause was identified as being a new virus, later named SARS-CoV-2. We can distinguish three clinical phases of the disease with a distinct pathogenesis, manifestations and prognosis. Here, we describe the case of a 45-year-old male, successfully treated for Coronavirus disease (COVID-19). The patient was feeling sick in early April 2020; he had a fever and pharyngodynia. When he came to our COVID hospital, his breathing was normal. The nasopharyngeal swab specimen turned out positive. High-resolution computed tomography (HRCT) showed mild interstitial pneumonia. The patient was admitted to our department and treated with hydroxychloroquine, ritonavir, darunavir, azithromycin and enoxaparin. On day seven of the disease, the patient's respiratory condition got worse as he was developing acute respiratory distress syndrome (ARDS). He was given tocilizumab and corticosteroids and was immediately treated with non-invasive mechanical ventilation (NIMV). His condition improved, and in the ensuing days, the treatment gradually switched to a high-flow nasal cannula (HFNC); after 18 days, the patient's clinical condition was good.The successful results we have been able to obtain are closely associated with avoidance of invasive ventilation that may lead to intensive care unit (ICU)-related superinfections. In our opinion, it is fundamental to understand that COVID-19 is a systemic disease that is a consequence of an overwhelming inflammatory response, which can cause severe medical conditions, even in young patients.


Subject(s)
Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Azithromycin/administration & dosage , Azithromycin/therapeutic use , COVID-19 , China , Coronavirus Infections/drug therapy , Coronavirus Infections/pathology , Darunavir/administration & dosage , Darunavir/therapeutic use , Disease Progression , Enoxaparin/administration & dosage , Enoxaparin/therapeutic use , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/therapeutic use , Male , Middle Aged , Noninvasive Ventilation , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/pathology , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , Ritonavir/administration & dosage , Ritonavir/therapeutic use
20.
Int J Infect Dis ; 97: 7-10, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-437018

ABSTRACT

OBJECTIVES: Given the high need and the absence of specific antivirals for treatment of COVID-19 (the disease caused by severe acute respiratory syndrome-associated coronavirus-2 [SARS-CoV-2]), human immunodeficiency virus (HIV) protease inhibitors are being considered as therapeutic alternatives. METHODS: Prezcobix/Rezolsta is a fixed-dose combination of 800 mg of the HIV protease inhibitor darunavir (DRV) and 150 mg cobicistat, a CYP3A4 inhibitor, which is indicated in combination with other antiretroviral agents for the treatment of HIV infection. There are currently no definitive data on the safety and efficacy of DRV/cobicistat for the treatment of COVID-19. The in vitro antiviral activity of darunavir against a clinical isolate from a patient infected with SARS-CoV-2 was assessed. RESULTS: DRV showed no antiviral activity against SARS-CoV-2 at clinically relevant concentrations (EC50 > 100 µM). Remdesivir, used as a positive control, demonstrated potent antiviral activity (EC50 = 0.38 µM). CONCLUSIONS: Overall, the data do not support the use of DRV for the treatment of COVID-19.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections , Darunavir/therapeutic use , Pandemics , Pneumonia, Viral , Antiviral Agents/therapeutic use , COVID-19 , Cell Line , Cell Survival/drug effects , Coronavirus Infections/drug therapy , Humans , Pneumonia, Viral/drug therapy , SARS-CoV-2
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