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1.
J Acquir Immune Defic Syndr ; 85(2): 239-243, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-787458

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 , 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
2.
Virus Res ; 286: 198057, 2020 09.
Article in English | MEDLINE | ID: covidwho-773200

ABSTRACT

The fight against the novel coronavirus pneumonia (namely COVID-19) that seriously harms human health is a common task for all mankind. Currently, development of drugs against the novel coronavirus (namely SARS-CoV-2) is quite urgent. Chinese medical workers and scientific researchers have found some drugs to play potential therapeutic effects on COVID-19 at the cellular level or in preliminary clinical trials. However, more fundamental studies and large sample clinical trials need to be done to ensure the efficacy and safety of these drugs. The adoption of these drugs without further testing must be careful. The relevant articles, news, and government reports published on the official and Preprint websites, PubMed and China National Knowledge Infrastructure (CNKI) databases from December 2019 to April 2020 were searched and manually filtered. The general pharmacological characteristics, indications, adverse reactions, general usage, and especially current status of the treatment of COVID-19 of those potentially effective drugs, including chemical drugs, traditional Chinese medicines (TCMs), and biological products in China were summarized in this review to guide reasonable medication and the development of specific drugs for the treatment of COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Drugs, Chinese Herbal/therapeutic use , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Amides/therapeutic use , Betacoronavirus/immunology , China/epidemiology , Chloroquine/therapeutic use , Coronavirus Infections/mortality , Coronavirus Infections/virology , Drug Combinations , Humans , Indoles/therapeutic use , Interferons/therapeutic use , Lopinavir/therapeutic use , Lung/drug effects , Lung/pathology , Lung/virology , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Pyrazines/therapeutic use , Ribavirin/therapeutic use , Ritonavir/therapeutic use , Survival Analysis
3.
Antimicrob Agents Chemother ; 64(9)2020 08 20.
Article in English | MEDLINE | ID: covidwho-654170

ABSTRACT

Previously, ivermectin (1 to 10 mg/kg of body weight) was shown to inhibit the liver-stage development of Plasmodium berghei in orally dosed mice. Here, ivermectin showed inhibition of the in vitro development of Plasmodium cynomolgi schizonts (50% inhibitory concentration [IC50], 10.42 µM) and hypnozoites (IC50, 29.24 µM) in primary macaque hepatocytes when administered as a high dose prophylactically but not when administered in radical cure mode. The safety, pharmacokinetics, and efficacy of oral ivermectin (0.3, 0.6, and 1.2 mg/kg) with and without chloroquine (10 mg/kg) administered for 7 consecutive days were evaluated for prophylaxis or radical cure of P. cynomolgi liver stages in rhesus macaques. No inhibition or delay to blood-stage P. cynomolgi parasitemia was observed at any ivermectin dose (0.3, 0.6, and 1.2 mg/kg). Ivermectin (0.6 and 1.2 mg/kg) and chloroquine (10 mg/kg) in combination were well-tolerated with no adverse events and no significant pharmacokinetic drug-drug interactions observed. Repeated daily ivermectin administration for 7 days did not inhibit ivermectin bioavailability. It was recently demonstrated that both ivermectin and chloroquine inhibit replication of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro Further ivermectin and chloroquine trials in humans are warranted to evaluate their role in Plasmodium vivax control and as adjunctive therapies against COVID-19 infections.


Subject(s)
Antimalarials/pharmacology , Chloroquine/pharmacology , Ivermectin/pharmacology , Liver/drug effects , Malaria/drug therapy , Plasmodium cynomolgi/drug effects , Animals , Antimalarials/blood , Antimalarials/pharmacokinetics , Biological Availability , Chloroquine/blood , Chloroquine/pharmacokinetics , Drug Administration Schedule , Drug Combinations , Drug Synergism , Female , Hepatocytes/drug effects , Hepatocytes/parasitology , Ivermectin/blood , Ivermectin/pharmacokinetics , Liver/parasitology , Macaca mulatta , Malaria/parasitology , Male , Parasitemia/drug therapy , Plasmodium cynomolgi/growth & development , Plasmodium cynomolgi/pathogenicity , Primary Cell Culture , Schizonts/drug effects , Schizonts/growth & development
4.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(8): 928-932, 2020 Aug.
Article in Chinese | MEDLINE | ID: covidwho-760964

ABSTRACT

OBJECTIVE: To describe the characteristics of liver damage in severe coronavirus disease 2019 (COVID-19) patients in Sichuan area and the effect of antiviral drugs on liver function. METHODS: The clinical data of severe COVID-19 patients admitted to Chengdu Public Health Clinical Medical Center from January 21 to February 24, 2020 were retrospectively collected, including demographic data, clinical manifestations and liver function changes within 1 week after admission to intensive care unit (ICU). The changes of liver function during the course of disease in severe COVID-19 patients were analyzed and summarized, and group analysis was performed. RESULTS: A total of 30 COVID-19 patients with complete clinical data were enrolled. The incidence of severe COVID-19 in elderly men was higher (60.0%), with median age of 61 (47, 79) years old, and those aged 80 or above accounted for 23.3%. The severe COVID-19 patients mainly presented with respiratory symptoms such as fever (96.7%), cough (80.0%) and dyspnea (66.7%). The alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) and prothrombin time (PT) of 30 patients were increased to various degrees within 1 week after ICU admission, and albumin (ALB) was decreased. (1) The patients were divided into two groups according to whether to take lopinavir/ritonavir (kaletra). It was shown that the incidence of liver dysfunction in patients taking kaletra was significantly higher than those who did not take kaletra (7-day abnormal rate of ALT was 54% vs. 33%, the abnormal rate of AST was 38% vs. 33%, the abnormal rate of TBil was 8% vs. 0%), but there were no statistical differences (all P > 0.05). (2) The patients were divided into normal dose group (500 mg, twice a day, n = 19) and reduced dose group (250 mg, twice a day, n = 5) according to the dosage of kaletra. It was shown that patients taking low-dose kaletra had a smaller effect on liver function within 1 week after ICU admission than those receiving normal dosage, and ALB, TBil in the reduced dose group were significantly lower than those in the normal dose group on the 2nd day after ICU admission [ALB (g/L): 33.3±2.0 vs. 37.5±4.0, TBil (µmol/L): 6.3±3.3 vs. 11.3±4.8, both P < 0.05]. CONCLUSIONS: Severe COVID-19 patients in Sichuan area suffered obvious liver damage in the early course of the disease and have a slower recovery. It is important to pay attention to avoid using drugs that can aggravate liver damage while treating the disease. If there is no alternative drug, liver protection treatment should be considered appropriately.


Subject(s)
Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Liver Diseases/virology , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , China/epidemiology , Coronavirus Infections/epidemiology , Drug Combinations , Humans , Liver Diseases/physiopathology , Lopinavir/therapeutic use , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Retrospective Studies , Ritonavir/therapeutic use , Severity of Illness Index , Treatment Outcome
5.
Medicine (Baltimore) ; 99(35): e21810, 2020 Aug 28.
Article in English | MEDLINE | ID: covidwho-740205

ABSTRACT

RATIONALE: The clinical manifestations of the SARS-CoV-2 infection are mainly respiratory but the virus can cause a variety of symptoms. Dermatological findings are less well-characterized. Data is scarce on their timing, type and correlation with the immune response. PATIENT CONCERNS: We present the case of SARS-CoV-2 infection in a previously healthy woman who presented with respiratory symptoms and developed anosmia, diarrhea, and an erythematous maculo-papular rash on day 15 from symptom onset. DIAGNOSIS: The nasopharyngeal swab tested by real time PCR for COVID-19 was positive. We interpreted this as a viral exanthema likely caused by an immune response to SARS-CoV-2 nucleotides. INTERVENTIONS: She was treated with Hydroxychloroquine, Azithromycin and Lopinavir/Ritonavir, and the rash with topical corticosteroids. OUTCOMES: All symptoms resolved except for anosmia which persisted for 6 weeks. At the 4- and 6-weeks follow-up the IgG titers for SARS-CoV-2 were high. LESSONS: We must consider that SARS-CoV-2 has a multi-organ tropism. In our case, the SARS-CoV-2 infection had lung, nasopharyngeal, neurological, digestive, and skin manifestations. Identifying the different manifestations is useful for understanding the extent of SARS-CoV-2 infection. We not only present a rare manifestation but also suggest that cutaneous manifestations may correlate with immunity.


Subject(s)
Azithromycin/administration & dosage , Betacoronavirus , Coronavirus Infections , Exanthema , Glucocorticoids/administration & dosage , Hydroxychloroquine/administration & dosage , Lopinavir/administration & dosage , Pandemics , Pneumonia, Viral , Ritonavir/administration & dosage , Administration, Topical , Adult , Antiviral Agents/administration & dosage , Betacoronavirus/immunology , Betacoronavirus/isolation & purification , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Drug Combinations , Exanthema/diagnosis , Exanthema/drug therapy , Exanthema/etiology , Exanthema/immunology , Female , Humans , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Symptom Assessment/methods , Treatment Outcome
6.
Signal Transduct Target Ther ; 5(1): 172, 2020 08 27.
Article in English | MEDLINE | ID: covidwho-733534

ABSTRACT

No effective drug treatments are available for coronavirus disease 2019 (COVID-19). Host-directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage, death, or long-term functional disability in survivors require clinical evaluation. We performed a parallel assigned controlled, non-randomized, phase 1 clinical trial to evaluate the safety of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) infusions in the treatment of patients with moderate and severe COVID-19 pulmonary disease. The study enrolled 18 hospitalized patients with COVID-19 (n = 9 for each group). The treatment group received three cycles of intravenous infusion of UC-MSCs (3 × 107 cells per infusion) on days 0, 3, and 6. Both groups received standard COVID-treatment regimens. Adverse events, duration of clinical symptoms, laboratory parameters, length of hospitalization, serial chest computed tomography (CT) images, the PaO2/FiO2 ratio, dynamics of cytokines, and IgG and IgM anti-SARS-CoV-2 antibodies were analyzed. No serious UC-MSCs infusion-associated adverse events were observed. Two patients receiving UC-MSCs developed transient facial flushing and fever, and one patient developed transient hypoxia at 12 h post UC-MSCs transfusion. Mechanical ventilation was required in one patient in the treatment group compared with four in the control group. All patients recovered and were discharged. Our data show that intravenous UC-MSCs infusion in patients with moderate and severe COVID-19 is safe and well tolerated. Phase 2/3 randomized, controlled, double-blinded trials with long-term follow-up are needed to evaluate the therapeutic use of UC-MSCs to reduce deaths and improve long-term treatment outcomes in patients with serious COVID-19.


Subject(s)
Antibodies, Viral/blood , Betacoronavirus/immunology , Cord Blood Stem Cell Transplantation/methods , Coronavirus Infections/therapy , Hematopoietic Stem Cells/virology , Mesenchymal Stem Cell Transplantation/methods , Pneumonia, Viral/therapy , Adult , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Betacoronavirus/pathogenicity , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Coronavirus Infections/virology , Drug Combinations , Female , Glucocorticoids/therapeutic use , Hematopoietic Stem Cells/drug effects , Hematopoietic Stem Cells/immunology , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Lopinavir , Male , Middle Aged , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Respiration, Artificial , Ritonavir , Severity of Illness Index , Treatment Outcome
7.
BMC Cardiovasc Disord ; 20(1): 389, 2020 08 26.
Article in English | MEDLINE | ID: covidwho-730201

ABSTRACT

BACKGROUND: Fulminant (life-threatening) COVID-19 can be associated with acute respiratory failure (ARF), multi-system organ failure and cytokine release syndrome (CRS). We present a rare case of fulminant COVID-19 associated with reverse-takotsubo-cardiomyopathy (RTCC) that improved with therapeutic plasma exchange (TPE). CASE PRESENTATION: A 40 year old previous healthy male presented in the emergency room with 4 days of dry cough, chest pain, myalgias and fatigue. He progressed to ARF requiring high-flow-nasal-cannula (flow: 60 L/minute, fraction of inspired oxygen: 40%). Real-Time-Polymerase-Chain-Reaction (RT-PCR) assay confirmed COVID-19 and chest X-ray showed interstitial infiltrates. Biochemistry suggested CRS: increased C-reactive protein, lactate dehydrogenase, ferritin and interleukin-6. Renal function was normal but lactate levels were elevated. Electrocardiogram demonstrated non-specific changes and troponin-I levels were slightly elevated. Echocardiography revealed left ventricular (LV) basal and midventricular akinesia with apex sparing (LV ejection fraction: 30%) and depressed cardiac output (2.8 L/min) consistent with a rare variant of stress-related cardiomyopathy: RTCC. His ratio of partial arterial pressure of oxygen to fractional inspired concentration of oxygen was < 120. He was admitted to the intensive care unit (ICU) for mechanical ventilation and vasopressors, plus antivirals (lopinavir/ritonavir), and prophylactic anticoagulation. Infusion of milrinone failed to improve his cardiogenic shock (day-1). Thus, rescue TPE was performed using the Spectra Optia™ Apheresis System equipped with the Depuro D2000 Adsorption Cartridge (Terumo BCT Inc., USA) without protective antibodies. Over 5 days he received daily TPE (each lasting 4 hours). His lactate levels, oxygenation, and LV function normalized and he was weaned off vasopressors. His inflammation markers improved, and he was extubated on day-7. RT-PCR was negative on day-17. He was discharged to home isolation in good condition. CONCLUSION: Stress-cardiomyopathy may complicate the course of fulminant COVID-19 with associated CRS. If inotropic therapy fails, TPE without protective antibodies may help rescue the critically ill patient.


Subject(s)
Antiviral Agents/therapeutic use , Cardiotonic Agents/therapeutic use , Coronavirus Infections/therapy , Cytokine Release Syndrome/therapy , Plasma Exchange , Pneumonia, Viral/therapy , Respiratory Distress Syndrome, Adult/therapy , Shock, Cardiogenic/therapy , Takotsubo Cardiomyopathy/therapy , Adult , Betacoronavirus , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/diagnosis , Drug Combinations , Echocardiography , Humans , Lopinavir/therapeutic use , Male , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Respiration, Artificial , Respiratory Distress Syndrome, Adult/etiology , Ritonavir/therapeutic use , Shock, Cardiogenic/etiology , Takotsubo Cardiomyopathy/diagnostic imaging , Takotsubo Cardiomyopathy/etiology
8.
Antimicrob Agents Chemother ; 64(9)2020 08 20.
Article in English | MEDLINE | ID: covidwho-729357

ABSTRACT

Evidence to support the use of steroids in coronavirus disease 2019 (COVID-19) pneumonia is lacking. We aim to determine the impact of steroid use for COVID-19 pneumonia on hospital mortality. We performed a single-center retrospective cohort study in a university hospital in Madrid, Spain, during March of 2020. To determine the role of steroids in in-hospital mortality, patients admitted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and treated with steroids were compared to patients not treated with steroids, and we adjusted with a propensity score for patients on steroid treatment. Survival times were compared using the log rank test. Different steroid regimens were compared and adjusted with a second propensity score. During the study period, 463 out of 848 hospitalized patients with COVID-19 pneumonia fulfilled inclusion criteria. Among them, 396 (46.7%) patients were treated with steroids and 67 patients were not. Global mortality was 15.1%. The median time to steroid treatment from symptom onset was 10 days (interquartile range [IQR], 8 to 13 days). In-hospital mortality was lower in patients treated with steroids than in controls (13.9% [55/396] versus 23.9% [16/67]; hazard ratio [HR], 0.51 [95% confidence interval, 0.27 to 0.96]; P = 0.044). Steroid treatment reduced mortality by 41.8% relative to the mortality with no steroid treatment (relative risk reduction, 0.42 [95% confidence interval, 0.048 to 0.65]). Initial treatment with 1 mg/kg of body weight/day of methylprednisolone versus steroid pulses was not associated with in-hospital mortality (13.5% [42/310] versus 15.1% [13/86]; odds ratio [OR], 0.880 [95% confidence interval, 0.449 to 1.726]; P = 0.710). Our results show that the survival of patients with SARS-CoV-2 pneumonia is higher in patients treated with glucocorticoids than in those not treated. Rates of in-hospital mortality were not different between initial regimens of 1 mg/kg/day of methylprednisolone and glucocorticoid pulses.


Subject(s)
Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Hydroxychloroquine/therapeutic use , Interferons/therapeutic use , Lopinavir/therapeutic use , Methylprednisolone/therapeutic use , Pneumonia, Viral/drug therapy , Ritonavir/therapeutic use , Aged , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/immunology , Cardiovascular Diseases/mortality , Cardiovascular Diseases/virology , Comorbidity , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Coronavirus Infections/virology , Diabetes Mellitus/drug therapy , Diabetes Mellitus/immunology , Diabetes Mellitus/mortality , Diabetes Mellitus/virology , Drug Administration Schedule , Drug Combinations , Drug Therapy, Combination , Dyslipidemias/drug therapy , Dyslipidemias/immunology , Dyslipidemias/mortality , Dyslipidemias/virology , Female , Hospitals, University , Humans , Intensive Care Units , Length of Stay/statistics & numerical data , Male , Middle Aged , Neoplasms/drug therapy , Neoplasms/immunology , Neoplasms/mortality , Neoplasms/virology , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Retrospective Studies , Survival Analysis
11.
Rheumatol Int ; 40(10): 1593-1598, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-713879

ABSTRACT

OBJECTIVE: To describe clinical characteristics of patients with rheumatic and musculoskeletal diseases (RMDs) and immunosuppressive therapies with Coronavirus disease 2019 (COVID-19) at an academic rheumatology center in Madrid and to identify baseline variables associated with a severe infection requiring hospitalization. METHODS: We identified SARS-CoV-2 positive cases by polymerase chain reaction performed at our center within an updated RMDs database in our clinic. Additional RMDs patients were identified when they contacted the clinic because of a positive infection. Data extraction included diagnosis, demographics, immunosuppressive treatment, comorbidities, and laboratory tests. Comparisons between patients with or without hospitalization were performed. Multivariate logistic regression was used to analyze associations between baseline variables and need for hospitalization. RESULTS: A total of 62 patients with COVID-19 and underlying RMDs were identified by April 24, 2020. Median age was 60.9 years, and 42% men. Forty-two patients required hospitalization; these were more frequently men, older and with comorbidities. There were no statistically significant between-group differences for rheumatologic diagnosis and for baseline use of immunosuppressive therapy except for glucocorticoids that were more frequent in hospitalized patients. Total deaths were 10 (16%) patients. In multivariate analysis, male sex (odds ratio [OR], 8.63; p = 0.018), previous lung disease (OR, 27.47; p = 0.042), and glucocorticoids use (> 5 mg/day) (OR, 9.95; p = 0.019) were significantly associated to hospitalization. CONCLUSION: Neither specific RMD diagnoses or exposures to DMARDs were associated with increased odds of hospitalization. Being male, previous lung disease and exposure to glucocorticoids were associated with higher odds of hospitalization in RMDs patients.


Subject(s)
Arthritis, Psoriatic/drug therapy , Arthritis, Rheumatoid/drug therapy , Coronavirus Infections/physiopathology , Glucocorticoids/therapeutic use , Hospitalization/statistics & numerical data , Immunosuppressive Agents/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Pneumonia, Viral/physiopathology , Aged , Anti-Bacterial Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antirheumatic Agents/therapeutic use , Antiviral Agents/therapeutic use , Arthritis, Psoriatic/complications , Arthritis, Psoriatic/epidemiology , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/epidemiology , Autoimmune Diseases/complications , Autoimmune Diseases/drug therapy , Autoimmune Diseases/epidemiology , Azithromycin/therapeutic use , Betacoronavirus , Comorbidity , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Drug Combinations , Female , Humans , Hydroxychloroquine/therapeutic use , Logistic Models , Lopinavir/therapeutic use , Lung Diseases/epidemiology , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/epidemiology , Male , Middle Aged , Multivariate Analysis , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Retrospective Studies , Ritonavir/therapeutic use , Severity of Illness Index , Sex Factors , Spain/epidemiology
12.
Oncology (Williston Park) ; 34(8): 317-319, 2020 08 12.
Article in English | MEDLINE | ID: covidwho-713075

ABSTRACT

A 78-year-old man had a medical history of hypertension, atrial fibrillation, chronic kidney disease, and metastatic castration-resistant prostate cancer (CRPC). He had progressed to first-line therapy for CRPC with abiraterone plus androgen-deprivation therapy (ADT) and as second-line therapy he was being treated with docetaxel, with biochemical progression in his last prostate specific antigen measurement. He was admitted to the hospital on April 2020, in the middle of the coronavirus disease 2019 (COVID-19) pandemic, because of painful bone lesions and deterioration of renal function.


Subject(s)
Anticoagulants/therapeutic use , Bone Neoplasms/drug therapy , Coronavirus Infections/therapy , Palliative Care , Pneumonia, Viral/therapy , Prostatic Neoplasms, Castration-Resistant/drug therapy , Respiratory Insufficiency/therapy , Aged , Androgen Antagonists/therapeutic use , Androstenes/therapeutic use , Antineoplastic Agents/therapeutic use , Betacoronavirus , Bone Density Conservation Agents/therapeutic use , Bone Neoplasms/complications , Bone Neoplasms/secondary , Cancer Pain/complications , Cancer Pain/therapy , Coronavirus Infections/complications , Disease Progression , Docetaxel/therapeutic use , Drug Combinations , Eligibility Determination , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Intensive Care Units/supply & distribution , Lopinavir/therapeutic use , Male , Oxygen Inhalation Therapy , Pandemics , Pneumonia, Viral/complications , Prostatic Neoplasms, Castration-Resistant/complications , Prostatic Neoplasms, Castration-Resistant/pathology , Renal Insufficiency , Respiratory Insufficiency/etiology , Reverse Transcriptase Polymerase Chain Reaction , Ritonavir/therapeutic use , Severity of Illness Index , Zoledronic Acid/therapeutic use
13.
HIV Med ; 21(8): 536-540, 2020 09.
Article in English | MEDLINE | ID: covidwho-707537

ABSTRACT

The unprecedented global scale of COVID-19 globally has triggered a race to discover interventions to reduce associated morbidity and mortality and rapid release of research findings prior to any degree of critical review. As with previous novel infection outbreaks, antiretrovirals are just one drug class that has been held up as a potential strategy for prophylaxis and treatment with scant evidence and risk of harm. Here we summarize the evidence for antiretrovirals to treat COVID-19 and, as a drug that has also been studied in HIV, hydroxychloroquine, and flag some of the pitfalls of using therapies that have not been evaluated robustly.


Subject(s)
Anti-Retroviral Agents/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Drug Repositioning , Pneumonia, Viral/drug therapy , Research/standards , Coronavirus Infections/prevention & control , Drug Combinations , Drug Repositioning/standards , Drug Repositioning/trends , Humans , Hydroxychloroquine/therapeutic use , Lopinavir/therapeutic use , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Research/trends , Ritonavir/therapeutic use , Tenofovir/therapeutic use , Time Factors
14.
Orv Hetil ; 161(32): 1310-1321, 2020 08.
Article in Hungarian | MEDLINE | ID: covidwho-706828

ABSTRACT

Due to the COVID-19 pandemic caused by infection with the novel, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), transplant medicine also had to face a new, hitherto unknown challenge. To be prepared for any possibility, we consider it important to summarize the current knowledge regarding COVID-19 of liver and kidney transplant patients. Very early reports from Spanish and French registry recorded fatality rates of 18.6% and 13%, respectively, in renal patients which suggests a moderately worse outcome compared to the general population. In patients with positive PCR test but not showing clinical signs, the reduction of immunosuppression is not advised. In the case of gastrointestinal or respiratory signs with fever, the discontinuation of mycophenolate or mTOR inhibitors is recommended with decrease of the trough levels of calcineurin inhibitors to the lowest effective limit. Stop (kidney transplanted patients) or decrease (liver transplanted patients) immunosuppression and maintain corticosteroids when pulmonal injury develops and consider anti-IL1 and anti-IL6 monoclonal antibody use when hyperinflammatory syndrome is evolving. No proven effective treatment for SARS-CoV-2 exists currently. The use of lopinavir/ritonavir should be avoided because of the severe drug interaction with calcineurin inhibitors. The efficacy and tolerability of hidroxychloroquin remains to be also questionable; enroll patients into clinical trial with remdesivir or favipiravir if available. COVID-19 is characterized by virus-induced endothelial dysfunction, procoagulant state and renin-angiotensin-aldosteron system imbalance. Early thromboprofilaxis combination with low-molecular-weight heparin and low-dose aspirin is strongly recommended with the maintenance of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-II-receptor blocker (ARB) therapy when they were prescribed earlier. Orv Hetil. 2020; 161(32): 1310-1321.


Subject(s)
Coronavirus Infections/complications , Kidney Transplantation , Liver Transplantation , Pneumonia, Viral/complications , Transplant Recipients , Adrenal Cortex Hormones/therapeutic use , Betacoronavirus , Calcineurin Inhibitors/adverse effects , Contraindications, Drug , Drug Combinations , Drug Interactions , Humans , Immunosuppression , Lopinavir/adverse effects , Pandemics , Ritonavir/adverse effects
15.
Curr Med Chem ; 27(27): 4536-4541, 2020.
Article in English | MEDLINE | ID: covidwho-704887

ABSTRACT

Here we report on the most recent updates on experimental drugs successfully employed in the treatment of the disease caused by SARS-CoV-2 coronavirus, also referred to as COVID-19 (COronaVIrus Disease-19). In particular, several cases of recovered patients have been reported after being treated with lopinavir/ritonavir [which is widely used to treat Human Immunodeficiency Virus (HIV) infection] in combination with the anti-flu drug oseltamivir. In addition, remdesivir, which has been previously administered to Ebola virus patients, has also proven effective in the U.S. against coronavirus, while antimalarial chloroquine and hydroxychloroquine, favipiravir and co-administered darunavir and umifenovir (in patient therapies) were also recently recorded as having anti-SARS-CoV-2 effects. Since the recoveries/deaths ratio in the last weeks significantly increased, especially in China, it is clear that the experimental antiviral therapy, together with the availability of intensive care unit beds in hospitals and rigorous government control measures, all play an important role in dealing with this virus. This also stresses the urgent need for the scientific community to devote its efforts to the development of other more specific antiviral strategies.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Amides , Betacoronavirus , China , Darunavir , Drug Combinations , Humans , Hydroxychloroquine , Indoles , Lopinavir , Pandemics , Pyrazines , Ritonavir
16.
Spinal Cord Ser Cases ; 6(1): 69, 2020 08 04.
Article in English | MEDLINE | ID: covidwho-697068

ABSTRACT

STUDY DESIGN: Observational case-control study. OBJECTIVE: Individuals with spinal cord injury (SCI) develop systemic physiological changes that could increase the risk of severe evolution of coronavirus disease 2019 (COVID-19) and result in atypical clinical features of COVID-19 with possible delay in both diagnosis and treatment. We evaluated differences in clinical features and evolution of COVID-19 between people with SCI and able-bodied individuals. SETTING: The study was conducted in an Italian inpatient rehabilitation referral center for individuals with SCI during the lockdown for the COVID-19 pandemic. METHODS: We compared clinical information between patients with SCI and able-bodied healthcare workers of the same center who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the nasopharyngeal swab polymerase chain reaction. RESULTS: Overall, 15 out of the 25 SCI patients admitted to the center and 17 out of the 69 healthcare workers tested positive for SARS-CoV-2. Patients with SCI exhibited a significantly more advanced age and a higher prevalence of comorbidities. Nevertheless, no significant differences in clinical expression of COVID-19 and treatment strategies were observed between the two groups. All hospitalized subjects were treated in nonintensive care units and no deaths occurred in either group. CONCLUSIONS: This study does not support the supposed notion that COVID-19 could exhibit atypical clinical features or a worse evolution in the frail population of people with SCI.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , Coronavirus Infections/therapy , Hydroxychloroquine/therapeutic use , Oxygen Inhalation Therapy , Pneumonia, Viral/therapy , Spinal Cord Injuries/physiopathology , Adult , Aged , Azithromycin/therapeutic use , Betacoronavirus , Case-Control Studies , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Coronavirus Infections/physiopathology , Drug Combinations , Enzyme Inhibitors/therapeutic use , Female , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Italy , Lopinavir/therapeutic use , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/physiopathology , Prognosis , Rehabilitation Centers , Ritonavir/therapeutic use , Spinal Cord Injuries/complications
17.
J Infect Public Health ; 13(9): 1187-1195, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-692147

ABSTRACT

The unprecedented challenge faced by mankind due to emergence of coronavirus 2019 (COVID-19) pandemic has obligated researchers across the globe to develop effective medicine for prevention and treatment of this deadly infection. The aim of this review is to compile recently published research articles on anti-COVID 19 management with their benefits and risk to facilitate decision making of the practitioners and policy makers. Unfortunately, clinical outcomes reported for antivirals are not consistent. Initial favorable reports on lopinavir/ritonavir contradicted by recent studies. Ostalmovir has conflicting reports. Short term therapy of remdesivir claimed to be beneficial. Favipiravir demonstrated good recovery in some of the cases of COVID-19. Umifenovir (Arbidol) was associated with reduction in mortality in few studies. Overall, until now, U.S. Food and Drug administration issued only emergency use authorization to remdesivir for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/therapeutic use , Alanine/therapeutic use , Amides/therapeutic use , Drug Combinations , Humans , Indoles/therapeutic use , Lopinavir/therapeutic use , Pandemics , Pyrazines/therapeutic use , Ritonavir/therapeutic use
18.
BMJ ; 370: m2980, 2020 07 30.
Article in English | MEDLINE | ID: covidwho-691120

ABSTRACT

OBJECTIVE: To compare the effects of treatments for coronavirus disease 2019 (covid-19). DESIGN: Living systematic review and network meta-analysis. DATA SOURCES: US Centers for Disease Control and Prevention COVID-19 Research Articles Downloadable Database, which includes 25 electronic databases and six additional Chinese databases to 20 July 2020. STUDY SELECTION: Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. METHODS: After duplicate data abstraction, a bayesian random effects network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. RESULTS: 23 randomised controlled trials were included in the analysis performed on 26 June 2020. The certainty of the evidence for most comparisons was very low because of risk of bias (lack of blinding) and serious imprecision. Glucocorticoids were the only intervention with evidence for a reduction in death compared with standard care (risk difference 37 fewer per 1000 patients, 95% credible interval 63 fewer to 11 fewer, moderate certainty) and mechanical ventilation (31 fewer per 1000 patients, 47 fewer to 9 fewer, moderate certainty). These estimates are based on direct evidence; network estimates for glucocorticoids compared with standard care were less precise because of network heterogeneity. Three drugs might reduce symptom duration compared with standard care: hydroxychloroquine (mean difference -4.5 days, low certainty), remdesivir (-2.6 days, moderate certainty), and lopinavir-ritonavir (-1.2 days, low certainty). Hydroxychloroquine might increase the risk of adverse events compared with the other interventions, and remdesivir probably does not substantially increase the risk of adverse effects leading to drug discontinuation. No other interventions included enough patients to meaningfully interpret adverse effects leading to drug discontinuation. CONCLUSION: Glucocorticoids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care. The effectiveness of most interventions is uncertain because most of the randomised controlled trials so far have been small and have important study limitations. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol is included as a supplement. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/isolation & purification , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Respiration, Artificial/statistics & numerical data , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Betacoronavirus/pathogenicity , Centers for Disease Control and Prevention, U.S./statistics & numerical data , China/epidemiology , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/mortality , Coronavirus Infections/virology , Databases, Factual/statistics & numerical data , Drug Combinations , Evidence-Based Medicine/methods , Evidence-Based Medicine/statistics & numerical data , Glucocorticoids/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Lopinavir/therapeutic use , Network Meta-Analysis , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Randomized Controlled Trials as Topic , Ritonavir/therapeutic use , Severity of Illness Index , Standard of Care , Treatment Outcome , United States/epidemiology
19.
Ann Rheum Dis ; 79(10): 1286-1289, 2020 10.
Article in English | MEDLINE | ID: covidwho-689316

ABSTRACT

OBJECTIVES: The outbreak of COVID-19 posed the issue of urgently identifying treatment strategies. Colchicine was considered for this purpose based on well-recognised anti-inflammatory effects and potential antiviral properties. In the present study, colchicine was proposed to patients with COVID-19, and its effects compared with 'standard-of-care' (SoC). METHODS: In the public hospital of Esine, northern Italy, 140 consecutive inpatients, with virologically and radiographically confirmed COVID-19 admitted in the period 5-19 March 2020, were treated with 'SoC' (hydroxychloroquine and/or intravenous dexamethasone; and/or lopinavir/ritonavir). They were compared with 122 consecutive inpatients, admitted between 19 March and 5 April 2020, treated with colchicine (1 mg/day) and SoC (antiviral drugs were stopped before colchicine, due to potential interaction). RESULTS: Patients treated with colchicine had a better survival rate as compared with SoC at 21 days of follow-up (84.2% (SE=3.3%) vs 63.6% (SE=4.1%), p=0.001). Cox proportional hazards regression survival analysis showed that a lower risk of death was independently associated with colchicine treatment (HR=0.151 (95% CI 0.062 to 0.368), p<0.0001), whereas older age, worse PaO2/FiO2, and higher serum levels of ferritin at entry were associated with a higher risk. CONCLUSION: This proof-of-concept study may support the rationale of use of colchicine for the treatment of COVID-19. Efficacy and safety must be determined in controlled clinical trials.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Colchicine/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Respiratory Distress Syndrome, Adult/drug therapy , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Betacoronavirus , Case-Control Studies , Cohort Studies , Coronavirus Infections/complications , Coronavirus Infections/mortality , Dexamethasone/therapeutic use , Drug Combinations , Enzyme Inhibitors/therapeutic use , Female , Hospitalization , Humans , Hydroxychloroquine/therapeutic use , Italy , Lopinavir/therapeutic use , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , Proof of Concept Study , Proportional Hazards Models , Respiratory Distress Syndrome, Adult/etiology , Respiratory Distress Syndrome, Adult/mortality , Ritonavir/therapeutic use , Survival Rate
20.
J Acquir Immune Defic Syndr ; 85(2): 239-243, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-682022

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 , 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
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