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2.
Curr HIV Res ; 19(4): 377-382, 2021.
Article in English | MEDLINE | ID: covidwho-1204159

ABSTRACT

BACKGROUND: The World Health Organization (WHO) announced the SARS-COV-2 disease pandemic on March 9, 2020. With the advent of this disease, another health burden was added to about 37.9 million people in the world who are infected with HIV and are suffering from various diseases. These people may be at serious risk of COVID-19. Information about the effects of COVID-19 on people living with HIV, is limited. CASE PRESENTATION: We reported a 61-year-old man who was a known case of HIV from 6 years ago that was being treated with HAART (highly active antiretroviral therapy). He also had a history of Hodgkin's lymphoma from 4 years ago who underwent autologous bone marrow transplantation (BMT) 2 weeks before given referral to our hospital. He complained of weakness, anorexia, and fever. RT-PCR for SARS-COV-2-RNA was positive in his nasopharyngeal and oropharyngeal swab. He was diagnosed with COVID-19 infection and treated with atazanavir. After one week, the patient discharged in a good general state. CONCLUSION: To the best of our knowledge, it is the first report of COVID-19 infection in an HIV positive patient after BMT in Iran. Despite his immunodeficiency, COVID-19 disease had mild manifestations and he had a good prognosis. We hope that our report and that of others can remain promising to doctors and HIV patients cross fingers for COVID-19 recovery.


Subject(s)
Atazanavir Sulfate/therapeutic use , Bone Marrow Transplantation , COVID-19/drug therapy , Comorbidity , HIV Infections/drug therapy , HIV Protease Inhibitors/therapeutic use , Hodgkin Disease/surgery , Humans , Iran , Male , Middle Aged , SARS-CoV-2 , Treatment Outcome
3.
J Infect Dis ; 224(Supplement_6): S631-S641, 2021 Dec 08.
Article in English | MEDLINE | ID: covidwho-1195718

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binding receptor ACE2 and the spike protein priming protease TMPRSS2 are coexpressed in human placentae. It is unknown whether their expression is altered in the context of HIV infection and antiretroviral therapy (ART). METHODS: We compared mRNA levels of SARS-CoV-2 cell-entry mediators ACE2, TMPRSS2, and L-SIGN by quantitative polymerase chain reaction in 105 placentae: 45 from pregnant women with HIV (WHIV) on protease inhibitor (PI)-based ART, 17 from WHIV on non-PI-based ART, and 43 from HIV-uninfected women. RESULTS: ACE2 levels were lower, while L-SIGN levels were higher, in placentae from WHIV on PI-based ART compared to those on non-PI-based ART and to HIV-uninfected women. TMPRSS2 levels were similar between groups. Black race was significantly associated with lower expression of ACE2 and higher expression of L-SIGN. ACE2 levels were significantly higher in placentae of female fetuses. CONCLUSIONS: We identified pregnant women of black race and WHIV on PI-based ART to have relatively lower expression of placental ACE2 than those of white race and HIV-uninfected women. This may potentially contribute to altered susceptibility to COVID-19 in these women, favorably by reduced viral entry or detrimentally by loss of ACE2 protection against hyperinflammation.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19 , Cell Adhesion Molecules/metabolism , HIV Infections/blood , Lectins, C-Type/metabolism , Placenta/metabolism , Receptors, Cell Surface/metabolism , SARS-CoV-2/physiology , Serine Endopeptidases/genetics , Adult , Angiotensin-Converting Enzyme 2/genetics , Antiretroviral Therapy, Highly Active , COVID-19/diagnosis , Case-Control Studies , Cell Adhesion Molecules/genetics , Female , HIV Infections/drug therapy , HIV Protease Inhibitors/therapeutic use , Humans , Lectins, C-Type/genetics , Pregnancy , RNA, Messenger , Real-Time Polymerase Chain Reaction , Receptors, Cell Surface/genetics
4.
J Acquir Immune Defic Syndr ; 85(2): 239-243, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-1165586

ABSTRACT

BACKGROUND: The effectiveness of lopinavir/ritonavir (LPV/r) and chloroquine treatment for COVID-19 has not been verified. METHODS: We conducted a retrospective study to summarize the clinical practices of nonsevere patients with COVID-19 receiving the standard care, LPV/r or chloroquine in Beijing Ditan Hospital from January 20 to March 26, 2020. The main outcome measurements include the changes of cycle threshold values of open reading frame 1 ab (ORF1ab) and nucleocapsid (N) genes by reverse transcriptase-polymerase chain reaction assay from day 1 to 7 after admission for patients receiving standard care or after treatment being initiated for patients receiving either LPV/r or chloroquine. The proportion of developing severe illness, fever duration and the time from symptom onset to chest computer tomography improvement, and negative conversion of nucleic acid were compared. RESULTS: Of the 129 patients included in the study, 59 received the standard care, 51 received LPV/r, and 19 received chloroquine. The demographics and baseline characteristics were comparable among the 3 groups. The median duration of fever, median time from symptom onset to chest computer tomography improvement, and negative conversion of the nucleic acid were similar among the 3 groups. The median increase in cycle threshold values of N and ORF1ab gene for patients receiving LPV/r or chloroquine or the standard care during the treatment course was 7.0 and 8.5, 8.0, and 7.6, 5.0, and 4.0, respectively. These figures were not found significantly different among the 3 groups. CONCLUSIONS: Antiviral therapy using LPV/r or chloroquine seemed not to improve the prognosis or shorten the clinical course of COVID-19.


Subject(s)
Chloroquine/therapeutic use , Coronavirus Infections/drug therapy , Lopinavir/therapeutic use , Pneumonia, Viral/drug therapy , Ritonavir/therapeutic use , Adult , Antimalarials/therapeutic use , COVID-19 , Chronic Disease , Coronavirus Infections/complications , Drug Combinations , Female , Fever , HIV Protease Inhibitors/therapeutic use , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Retrospective Studies , Treatment Outcome , Young Adult
5.
Turk J Med Sci ; 51(4): 1624-1630, 2021 08 30.
Article in English | MEDLINE | ID: covidwho-1138801

ABSTRACT

Background/aim: SARS-CoV-2, a ribonucleic acid coronavirus, rapidly spread worldwide within a short timeframe. Although different antiviral, antiinflammatory, and immunomodulatory drugs are used, current evidence is insufficient as to which drug is more efficient. Our study compared favipiravir and lopinavir/ritonavir (LPV/RTV) therapies in inpatient care for coronavirus disease 2019 (COVID-19) pneumonia. Materials and methods: Demographic data, test results, treatments, and latest status of patients receiving inpatient COVID-19 pneumonia therapy were recorded. The initial favipiravir and LPV/RTV receiving groups were compared regarding the need for intensive care units (ICU) and mortality. Logistic regression analysis was performed by including variables showing significant differences as a result of paired comparisons into the model. Results: Of the 204 patients with COVID-19 pneumonia, 59 (28.9%), 131 (64.2%), and 14 were administered LPV/RTV, favipiravir, and favipiravir with LPV/RTV, respectively. No difference was found in age, sex, presence of comorbidity, and tocilizumab, systemic corticosteroid, and plasma therapy use between patients administered with these three different treatment regimens. The mean mortality age of the patients was 71 ± 14.3 years, which was substantially greater than that of the survivors (54.2 ± 15.5 years). Compared with patients administered with LPV/RTV, ICU admission and mortality rates were lower in patients administered with favipiravir. CK-MB, AST, CRP, LDH, and creatinine levels were higher, whereas lymphocyte counts were lower in patients who died. Age, AST, CRP, LDH, and neutrophil counts were higher in patients needing ICU, and eosinophil and lymphocyte counts were significantly lower. Logistic regression analysis showed that favipiravir use independently decreased mortality (p = 0.006). Conclusion: The use of favipiravir was more effective than LPV/RTV in reducing mortality in hospitalized patients with COVID-19.


Subject(s)
Amides/therapeutic use , COVID-19/drug therapy , Lopinavir/therapeutic use , Pyrazines/therapeutic use , Ritonavir/therapeutic use , Aged , Antiviral Agents/therapeutic use , Drug Therapy, Combination/methods , Female , HIV Protease Inhibitors/therapeutic use , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
6.
Eur J Clin Pharmacol ; 77(9): 1297-1307, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1116615

ABSTRACT

AIMS: SARS-CoV-2 is a single-stranded RNA virus which is part of the ß-coronavirus family (like SARS 2002 and MERS 2012). The high prevalence of hospitalization and mortality, in addition to the lack of vaccines and therapeutics, forces scientists and clinicians around the world to evaluate new therapeutic options. One strategy is the repositioning of already known drugs, which were approved drugs for other indications. SUBJECT AND METHOD: SARS-CoV-2 entry inhibitors, RNA polymerase inhibitors, and protease inhibitors seem to be valuable targets of research. At the beginning of the pandemic, the ClinicalTrials.gov webpage listed n=479 clinical trials related to the antiviral treatment of SARS-CoV-2 (01.04.2020, "SARS-CoV-2," "COVID-19," "antivirals," "therapy"), of which n=376 are still accessible online in January 2021 (10.01.2021). Taking into account further studies not listed in the CTG webpage, this narrative review appraises HIV protease inhibitors and nucleos(t)ide RNA polymerase inhibitors as promising candidates for the treatment of COVID-19. RESULTS: Lopinavir/ritonavir, darunavir/cobicistat, remdesivir, tenofovir-disoproxilfumarate, favipriravir, and sofosbuvir are evaluated in clinical studies worldwide. Study designs show a high variability and results often are contradictory. Remdesivir is the drug, which is deployed in nearly 70% of the reviewed clinical trials, followed by lopinavir/ritonavir, favipiravir, ribavirine, and sofosbuvir. DISCUSSION: This review discusses the pharmacological/clinical background and questions the rationale and study design of clinical trials with already approved HIV protease inhibitors and nucleos(t)ide RNA polymerase inhibitors which are repositioned during the SARS-CoV-2 pandemic worldwide. Proposals are made for future study design and drug repositioning of approved antiretroviral compounds.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Drug Repositioning , ATP Binding Cassette Transporter, Subfamily B, Member 1/drug effects , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Antiviral Agents/pharmacology , Clinical Trials as Topic , Drug Combinations , Drug Interactions , HIV Protease Inhibitors/pharmacology , HIV Protease Inhibitors/therapeutic use , Humans , Nucleosides/analogs & derivatives , Nucleotides/pharmacology , Nucleotides/therapeutic use , Oxygen/blood , SARS-CoV-2
7.
Int Immunopharmacol ; 92: 107329, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1014566

ABSTRACT

Interferon Beta-1a (IFN-ß1-a), an immunomodulatory mediator with antiviral effects, has shown in vivo and in vitro activities especially on coronavirus including SARS-CoV-2. COVID-19 defined as the disease caused by infection with SARS-CoV-2. The virus has been illustrated inhibits the production of IFN-ß1-a from inflammatory cells. We conducted a retrospective study of all adult confirmed COVID-19 hospitalized patients who received combination of three doses of 12 million international units of IFN-ß1-a and Lopinavir 400 mg and Ritonavir 100 mg every 12 h (case group) for 14 days besides standard care and age- and sex- matched COVID-19 patients with receiving lopinavir/ritonavir (control group) at Masih Daneshvari Hospital as a designated hospital for COVID-19 between Feb 19 and Apr 30, 2020. Multivariate analysis was done to determine the impact of IFN-ß1-a on outcome and all-cause mortality. 152 cases in IFN-ß1-a group and 304 cases as control group were included. IFN-ß1-a group stayed at hospital longer and required noninvasive ventilation more than control group (13 vs. 6 days, p = 0.001) and (34% vs. 24%, p = 0.04), respectively. During treatment, 57 (12.5%) patients died. The death rate in case and control groups was 11% and 13% respectively. In multivariate analysis, not receiving IFN-ß1-a (HR 5.12, 95% CI: 2.77-9.45), comorbidity (HR 2.28, 95% CI: 1.13-4.60) and noninvasive ventilation (HR 2.77, 95% CI: 1.56-4.93) remained significantly associated with all-cause mortality. In this study, risk of death decreased by using IFN-ß1-a in COVID-19 patients. More clinical study will be necessary to measure efficacy of IFN-ß1-a in COVID-19 treatment.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , HIV Protease Inhibitors/therapeutic use , Interferon-beta/therapeutic use , Lopinavir/therapeutic use , Ritonavir/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Drug Combinations , Female , Humans , Interferon-beta/administration & dosage , Lopinavir/administration & dosage , Male , Middle Aged , Retrospective Studies , Ritonavir/administration & dosage , Young Adult
8.
J Electrocardiol ; 64: 30-35, 2021.
Article in English | MEDLINE | ID: covidwho-972123

ABSTRACT

BACKGROUND: Administration of Hydroxychloroquine and Azithromycin in patients with coronavirus disease 2019 (COVID-19) prolongs QTc corrected interval (QTc). The effect and safety of Lopinavir/Ritonavir in combination with these therapies have seldom been studied. OBJECTIVES: Our aim was to evaluate changes in QTc in patients receiving double (Hydroxychloroquine + Azithromycin) and triple therapy (Hydroxychloroquine + Azithromycin + Lopinavir/Ritonavir) to treat COVID-19. Secondary outcome was the incidence of in-hospital all-cause mortality. METHODS: Patients under treatment with double (DT) and triple therapy (TT) for COVID-19 were consecutively included in this prospective observational study. Serial in-hospital electrocardiograms were performed to measure QTc at baseline and during therapy. RESULTS: 168 patients (±66.2 years old) were included: 32.1% received DT and 67.9% received TT. The mean baseline QTc was 410.33 ms. Patients under DT and TT prolonged QTc interval respect baseline values (p < 0.001), without significant differences between both therapy groups (p = 0.748). Overall, 33 patients (19.6%) had a peak QTc and/or an increase QTc 60 ms from baseline, with a higher prevalence among those with hypokalemia (p = 0.003). All-cause mortality was similar between both strategy groups (p = 0.093) and high risk QTc prolongation was no related to clinical events in this series. CONCLUSIONS: DT and TT prolong the QTc in patients with COVID-19. Addition of Lopinavir/Ritonavir on top of Hydroxychloroquine and Azithromycin did not increase QTc compared to DT.


Subject(s)
Azithromycin/pharmacology , COVID-19/physiopathology , Electrocardiography/drug effects , Hydroxychloroquine/pharmacology , Lopinavir/pharmacology , Ritonavir/pharmacology , Aged , Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Drug Therapy, Combination , Female , HIV Protease Inhibitors/pharmacology , HIV Protease Inhibitors/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Kaplan-Meier Estimate , Lopinavir/therapeutic use , Male , Middle Aged , Prospective Studies , Ritonavir/therapeutic use
9.
BMC Infect Dis ; 20(1): 824, 2020 Nov 11.
Article in English | MEDLINE | ID: covidwho-917920

ABSTRACT

BACKGROUND: In December 2019, the novel coronavirus disease 2019 (COVID-19) emerged in Wuhan, Hubei Province, China. It rapidly spread and many cases were identified in multiple countries, posing a global health problem. Here, we report the first patient cured of COVID-19 infection in Changsha, China, and the symptoms, diagnosis, treatment, and management of this patient are all described in this report. CASE PRESENTATION: A 57-year-old woman developed cough and fever after returning to Changsha from Wuhan on January 9, 2020. She tested positive for COVID-19 infection, a diagnosis which was supported by chest CT. The patient was treated with lopinavir and ritonavir tablets and interferon alfa-2b injection. A low dose of glucocorticoids was used for a short period to control bilateral lung immune response, and this patient avoided being crushed by cytokine storms that might have occurred. The clinical condition of this patient improved, and a COVID-19 assay conducted on January 25, 2020 generated negative results. This patient recovered and was discharged on January 30, 2020. CONCLUSIONS: Currently, there are numerous reports on COVID-19 infections focusing on the disease's epidemiological and clinical characteristics. This case describes the symptoms, diagnosis, treatment, and management of a patient cured of COVID-19 infection, which may serve as reference for future cases, while further studies are needed.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/drug therapy , Glucocorticoids/therapeutic use , HIV Protease Inhibitors/therapeutic use , Interferon alpha-2/therapeutic use , Lopinavir/therapeutic use , Pneumonia, Viral/drug therapy , Ritonavir/therapeutic use , COVID-19 , China , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Cough , Female , Fever , Humans , Lung/diagnostic imaging , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Tomography, X-Ray Computed , Treatment Outcome
11.
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
12.
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
13.
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
15.
Mult Scler Relat Disord ; 43: 102216, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-419863

ABSTRACT

The new severe acute respiratory syndrome- coronavirus 2 is reported to affect the nervous system. Among the reports of the various neurological manifestations, there are a few documented specific processes to explain the neurological signs. We report a para-infectious encephalitis patient with clinical, laboratory, and imaging findings during evolution and convalescence phase of coronavirus infection. This comprehensive overview can illuminate the natural history of similar cases. As the two previously reported cases of encephalitis associated with this virus were not widely discussed regarding the treatment, we share our successful approach and add some recommendations about this new and scarce entity.


Subject(s)
Consciousness Disorders/physiopathology , Coronavirus Infections/physiopathology , Encephalitis/physiopathology , Glucocorticoids/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Methylprednisolone/therapeutic use , Pneumonia, Viral/physiopathology , Seizures/physiopathology , Adult , Anti-Bacterial Agents/therapeutic use , Anticonvulsants/therapeutic use , Atazanavir Sulfate/therapeutic use , Betacoronavirus , Brain/diagnostic imaging , COVID-19 , Consciousness Disorders/diagnostic imaging , Consciousness Disorders/etiology , Consciousness Disorders/therapy , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/therapy , Diffusion Magnetic Resonance Imaging , Disease Progression , Encephalitis/diagnostic imaging , Encephalitis/etiology , Encephalitis/therapy , Female , HIV Protease Inhibitors/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Intensive Care Units , Levetiracetam/therapeutic use , Lung/diagnostic imaging , Magnetic Resonance Imaging , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/therapy , Pons/diagnostic imaging , Respiration, Artificial , SARS-CoV-2 , Seizures/drug therapy , Seizures/etiology , Temporal Lobe/diagnostic imaging , Thalamus/diagnostic imaging , Tomography, X-Ray Computed
16.
Future Oncol ; 16(20): 1425-1432, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-260506

ABSTRACT

Background: We describe cancer patients with coronavirus disease-2019 (COVID-19) infection treated at the Piacenza's general hospital (north Italy). Materials & methods: 25 cancer patients infected by COVID-19 admitted at the Piacenza's general hospital from 21 February to 18 March 2020. Outcome from the infection were compared with infected noncancer patients. Results: 20 patients (80%) were treated with antiviral therapy and hydroxychloroquine and five (20%) received hydroxychloroquine alone. Nine (36%) patients died, while 16 (64%) overcome the infection. In the control group the mortality was 16.13% and the overcome from infection was 83.87%. Conclusion: Mortality for COVID-19 was greater in cancer patients when compared with noncancer patients, worse prognosis for older age, women and patients treated with hydroxychloroquine alone. However, the comparisons did not reach statistical significance in most cases. This could be due to the small sample size that is the main limitation of the study.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Coronavirus Infections/mortality , Hydroxychloroquine/therapeutic use , Neoplasms/mortality , Pneumonia, Viral/drug therapy , Pneumonia, Viral/mortality , Age Factors , Aged , Aged, 80 and over , Azithromycin/therapeutic use , Betacoronavirus , COVID-19 , Ceftriaxone/therapeutic use , Cobicistat/therapeutic use , Darunavir/therapeutic use , Drug Therapy, Combination , Female , HIV Protease Inhibitors/therapeutic use , Humans , Italy , Lopinavir/therapeutic use , Male , Methylprednisolone/therapeutic use , Middle Aged , Neoplasms/drug therapy , Pandemics , Ritonavir/therapeutic use , SARS-CoV-2
17.
Acta Ophthalmol ; 98(8): 859-863, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-260153

ABSTRACT

BACKGROUND: The current outbreak of COVID-19 has spread rapidly all over the world. Respiratory droplets and contaction with infected patients are the two major transmission routes. However, the value of tear virus nucleic acid is still not clear. We dynamic detected the SARS-CoV-2 in eye sample of one COVID-19 patient with obstruction of common lacrimal ducts. METHODS: Besides the routine examination, nasopharyngeal and eye swab were continuously measured by polymerase chain reaction assay and next-generation sequencing (NGS). Gene detection was performed for drug use guidance, and flow cytometry was performed to analyse the lymphocyte subsets. RESULTS: Nasopharyngeal swabs were positive for 22 days, but eye swabs were still continuously positive for 2 weeks after nasopharyngeal swabs turned negative. The low level of lymphocyte and the high level IL-6 lasted for almost 4 weeks, then became near normal. Next-generation sequencing (NGS) confirmed the existing of SARS-CoV-2, HSV1 and HHV6B virus nucleic acid. The gene detection for drug use guidance showed the genetic locus ABCB1 (3435T>C) rs1045642 belonged to type CC and it mean the efficiency of lopinavir-ritonavir would be significantly decreased. The flow cytometry of lymphocyte subsets showed PD-1+  CD95+ cells was accounting for 94.8% in CD3+  CD8+ T subset and for 94.8% in CD3+  TCRγδ+ T subset. CONCLUSIONS: As obstruction of common lacrimal duct, positively detection in one eye for 2 weeks more after nasopharyngeal swab became negative. More eye swabs should be collected from COVID-19 patients, especially from those immunocompromised, those with eye symptoms and those had a history of ocular diseases.


Subject(s)
COVID-19/diagnosis , Conjunctiva/virology , Eye Infections, Viral/diagnosis , Herpesvirus 1, Human/isolation & purification , Herpesvirus 6, Human/isolation & purification , Lacrimal Duct Obstruction/diagnosis , SARS-CoV-2/isolation & purification , Tears/virology , Aged , Anti-Bacterial Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Conjunctivitis, Viral/diagnosis , Drug Therapy, Combination , Eye Infections, Viral/drug therapy , Eye Infections, Viral/virology , Flow Cytometry , HIV Protease Inhibitors/therapeutic use , Herpes Simplex/diagnosis , Herpes Simplex/drug therapy , Herpes Simplex/virology , Herpesvirus 1, Human/genetics , Herpesvirus 6, Human/genetics , High-Throughput Nucleotide Sequencing , Humans , Lacrimal Duct Obstruction/drug therapy , Lacrimal Duct Obstruction/virology , Lopinavir/therapeutic use , Male , Medicine, Chinese Traditional , Moxifloxacin/therapeutic use , Nasopharynx/virology , Nucleic Acids/genetics , Polymerase Chain Reaction , RNA, Viral/genetics , Ritonavir/therapeutic use , Roseolovirus Infections/diagnosis , Roseolovirus Infections/drug therapy , Roseolovirus Infections/virology , SARS-CoV-2/genetics
18.
Travel Med Infect Dis ; 35: 101646, 2020.
Article in English | MEDLINE | ID: covidwho-47222

ABSTRACT

BACKGROUND: The COVID-19 has now been declared a global pandemic by the World Health Organization. There is an emergent need to search for possible medications. METHOD: Utilization of the available sequence information, homology modeling, and in slico docking a number of available medications might prove to be effective in inhibiting the SARS-CoV-2 two main drug targets, the spike glycoprotein, and the 3CL protease. RESULTS: Several compounds were determined from the in silico docking models that might prove to be effective inhibitors for SARS-CoV-2. Several antiviral medications: Zanamivir, Indinavir, Saquinavir, and Remdesivir show potential as and 3CLPRO main proteinase inhibitors and as a treatment for COVID-19. CONCLUSION: Zanamivir, Indinavir, Saquinavir, and Remdesivir are among the exciting hits on the 3CLPRO main proteinase. It is also exciting to uncover that Flavin Adenine Dinucleotide (FAD) Adeflavin, B2 deficiency medicine, and Coenzyme A, a coenzyme, may also be potentially used for the treatment of SARS-CoV-2 infections. The use of these off-label medications may be beneficial in the treatment of the COVID-19.


Subject(s)
Betacoronavirus/chemistry , Coronavirus Infections/virology , Cysteine Endopeptidases/chemistry , Drug Discovery/methods , Pneumonia, Viral/virology , Spike Glycoprotein, Coronavirus/chemistry , Viral Nonstructural Proteins/chemistry , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/chemistry , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/chemistry , Alanine/therapeutic use , Binding Sites , COVID-19 , Coronavirus 3C Proteases , Coronavirus Infections/drug therapy , HIV Protease Inhibitors/chemistry , HIV Protease Inhibitors/therapeutic use , Humans , Indinavir/chemistry , Indinavir/therapeutic use , Molecular Docking Simulation , Off-Label Use , Pandemics , Pneumonia, Viral/drug therapy , SARS-CoV-2 , Saquinavir/chemistry , Saquinavir/therapeutic use , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Structural Homology, Protein , Viral Nonstructural Proteins/antagonists & inhibitors , Zanamivir/chemistry , Zanamivir/therapeutic use
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