Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 356
Filter
Add filters

Year range
1.
Int J Mol Sci ; 21(14)2020 Jul 14.
Article in English | MEDLINE | ID: covidwho-649852

ABSTRACT

Effective treatment of retinal diseases with adeno-associated virus (AAV)-mediated gene therapy is highly dependent on the proportion of successfully transduced cells. However, due to inflammatory reactions at high vector doses, adjunctive treatment may be necessary to enhance the therapeutic outcome. Hydroxychloroquine and chloroquine are anti-malarial drugs that have been successfully used in the treatment of autoimmune diseases. Evidence suggests that at high concentrations, hydroxychloroquine and chloroquine can impact viral infection and replication by increasing endosomal and lysosomal pH. This effect has led to investigations into the potential benefits of these drugs in the treatment of viral infections, including human immunodeficiency virus and severe acute respiratory syndrome coronavirus-2. However, at lower concentrations, hydroxychloroquine and chloroquine appear to exert immunomodulatory effects by inhibiting nucleic acid sensors, including toll-like receptor 9 and cyclic GMP-AMP synthase. This dose-dependent effect on their mechanism of action supports observations of increased viral infections associated with lower drug doses. In this review, we explore the immunomodulatory activity of hydroxychloroquine and chloroquine, their impact on viral infections, and their potential to improve the efficacy and safety of retinal gene therapy by reducing AAV-induced immune responses. The safety and practicalities of delivering hydroxychloroquine into the retina will also be discussed.


Subject(s)
Chloroquine/therapeutic use , Genetic Therapy , Hydroxychloroquine/therapeutic use , Retinal Diseases/therapy , Virus Diseases/drug therapy , Animals , Betacoronavirus/drug effects , Chloroquine/pharmacology , Dependovirus/genetics , Humans , Hydroxychloroquine/pharmacology , Immunomodulation/drug effects , Retinal Diseases/pathology
2.
Vestn Oftalmol ; 136(4. Vyp. 2): 265-271, 2020.
Article in Russian | MEDLINE | ID: covidwho-745625

ABSTRACT

Coronavirus infection is currently en extremely relevant scientific topic due to the emergence of a new serotype that causes a condition identified as Severe Acute Respiratory Syndrome (SARS)-COV-2. Chloroquine and hydroxychloroquine have a long history of use against other infectious diseases, they are available and inexpensive, so the possibility of using them in vivo and in vitro to suppress the infectious agent was examined. Despite the noted therapeutic potential of these drugs, it was necessary to take into account the toxicological aspects that dictate the importance of rational use of 4-aminoquinoline derivatives. This review analyzes literature on the development patterns of hydroxychloroquine retinopathy, basic principles of diagnosis and differentiation of this condition from other types of retinal pathology.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Diagnosis, Differential , Humans , Hydroxychloroquine/therapeutic use , Pandemics
3.
MMWR Morb Mortal Wkly Rep ; 69(35): 1210-1215, 2020 Sep 04.
Article in English | MEDLINE | ID: covidwho-745358

ABSTRACT

Hydroxychloroquine and chloroquine, primarily used to treat autoimmune diseases and to prevent and treat malaria, received national attention in early March 2020, as potential treatment and prophylaxis for coronavirus disease 2019 (COVID-19) (1). On March 20, the Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for chloroquine phosphate and hydroxychloroquine sulfate in the Strategic National Stockpile to be used by licensed health care providers to treat patients hospitalized with COVID-19 when the providers determine the potential benefit outweighs the potential risk to the patient.* Following reports of cardiac and other adverse events in patients receiving hydroxychloroquine for COVID-19 (2), on April 24, 2020, FDA issued a caution against its use† and on June 15, rescinded its EUA for hydroxychloroquine from the Strategic National Stockpile.§ Following the FDA's issuance of caution and EUA rescindment, on May 12 and June 16, the federal COVID-19 Treatment Guidelines Panel issued recommendations against the use of hydroxychloroquine or chloroquine to treat COVID-19; the panel also noted that at that time no medication could be recommended for COVID-19 pre- or postexposure prophylaxis outside the setting of a clinical trial (3). However, public discussion concerning the effectiveness of these drugs on outcomes of COVID-19 (4,5), and clinical trials of hydroxychloroquine for prophylaxis of COVID-19 continue.¶ In response to recent reports of notable increases in prescriptions for hydroxychloroquine or chloroquine (6), CDC analyzed outpatient retail pharmacy transaction data to identify potential differences in prescriptions dispensed by provider type during January-June 2020 compared with the same period in 2019. Before 2020, primary care providers and specialists who routinely prescribed hydroxychloroquine, such as rheumatologists and dermatologists, accounted for approximately 97% of new prescriptions. New prescriptions by specialists who did not typically prescribe these medications (defined as specialties accounting for ≤2% of new prescriptions before 2020) increased from 1,143 prescriptions in February 2020 to 75,569 in March 2020, an 80-fold increase from March 2019. Although dispensing trends are returning to prepandemic levels, continued adherence to current clinical guidelines for the indicated use of these medications will ensure their availability and benefit to patients for whom their use is indicated (3,4), because current data on treatment and pre- or postexposure prophylaxis for COVID-19 indicate that the potential benefits of these drugs do not appear to outweigh their risks.


Subject(s)
Chloroquine/therapeutic use , Hydroxychloroquine/therapeutic use , Practice Patterns, Physicians'/statistics & numerical data , Specialization/statistics & numerical data , Coronavirus Infections/drug therapy , Female , Humans , Male , Treatment Outcome , United States
4.
Trials ; 21(1): 754, 2020 Aug 31.
Article in English | MEDLINE | ID: covidwho-742452

ABSTRACT

OBJECTIVES: To evaluate the effect of the combination of hydroxychloroquine (HCQ) and standard personal protective equipment (PPE) compared to the use of standard personal protective equipment alone on the proportion of laboratory confirmed COVID-19 infections among frontline healthcare workers(HCWs) in India TRIAL DESIGN: HOPE is an investigator initiated multi-centre open-label parallel group randomized controlled trial. PARTICIPANTS: All HCWs currently working in an environment with direct exposure to patients with confirmed COVID-19 infection are eligible to participate in the trial. The trial aims to be conducted across 20-30 centres (public and private hospitals) in India. HCWs who decline consent, who have a confirmed COVID-19 infection, those who are already on chloroquine/HCQ for any indication, or if pregnant or breast-feeding, or have known QT prolongation or are on medications that when taken with HCQ can prolong the QTc will be excluded. INTERVENTION AND COMPARATOR: The interventions to be compared in this trial are standard practice (use of recommended PPE) and HCQ plus standard practice. In the standard practice arm, HCWs will use recommended PPE as per institutional guidelines and based on their roles. They will be discouraged from taking HCQ to prevent contamination and contacted every week for the duration of the study to ascertain if they have taken any HCQ. Any such use will be reported as a protocol violation. In the intervention arm, HCWs will be administered 800mg of HCQ as a loading dose on the day of randomization (as two 400mg doses 12hrs apart) and subsequently continued on 400mg once a week for 12 weeks. This will be in addition to the use of recommended PPE as per institutional guidelines and based on their roles. HCWs will collect the drug once every week from designated research and pharmacy staff at site. A weekly phone reminder will be provided to participants in this arm to ensure compliance. An ECG will be performed between 4-6 weeks in this arm and if the QTc is prolonged (greater than 450milliseconds), the drug will be stopped. Follow-up will however continue. Participants in both arms will receive a weekly phone call for evaluation of the primary outcome, to monitor protocol compliance and development of any adverse events (in the HCQ group). MAIN OUTCOMES: Participants will be followed on a weekly basis. The primary outcome is the proportion of HCWs developing laboratory confirmed COVID-19 infection within 6 months of randomization. We will also evaluate a number of secondary outcomes, including hospitalization related to suspected/confirmed COVID-19 infection, intensive care unit or high-dependency unit admission due to suspected/confirmed COVID-19 infection, all-cause mortality, need for organ support ( non-invasive or invasive ventilation, vasopressors and renal replacement therapy), ICU and hospital length of stay, readmission, days off work and treatment-related adverse events. RANDOMISATION: Randomisation will be conducted through a password-protected, secure website using a central, computer-based randomisation program. Randomisation will be stratified by participating institutions and by the role of HCW - nursing, medical and other. Participants will be randomised 1:1 to either standard practice only or HCQ plus standard practice. Allocation concealment is maintained by central web-based randomisation BLINDING (MASKING): This is an unblinded study: study assigned treatment will be known to the research team and participant. Bias will be mitigated through an objective end point (laboratory confirmed COVID-19 infection). NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 6,950 HCWs will be enrolled (3475 to the intervention) and (3475 to the standard practice group) to detect a 25% relative reduction, or 2.5% absolute reduction, in the infection rate from an estimated baseline infection rate of 10%, with 80% statistical power using a two-sided test at 5% level of significance. Available data from China and Italy indicate that the rate of infection among frontline healthcare workers varies between 4% to 12%. We therefore assumed a baseline infection rate of 10% among HCWs. This sample size allows for a potential loss to follow-up rate of 10% and a potential non-compliance rate of 10% in both the treatment and control arms. TRIAL STATUS: HOPE protocol version 3.0 dated June 3rd 2020. Recruitment started on 29th June 2020 and currently 56 participants have been enrolled. Planned completion of enrolment is January 31st 2021. TRIAL REGISTRATION: Clinical Trials Registry of India: CTRI/2020/05/025067 (prospectively registered) Date of registration: 6th May 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expedited dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Subject(s)
Coronavirus Infections/prevention & control , Enzyme Inhibitors/therapeutic use , Health Personnel , Hydroxychloroquine/therapeutic use , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Occupational Diseases/prevention & control , Pandemics/prevention & control , Personal Protective Equipment , Pneumonia, Viral/prevention & control , Betacoronavirus , Chemoprevention , Coronavirus Infections/transmission , Humans , India , Pneumonia, Viral/transmission
5.
Adv Biol Regul ; 77: 100745, 2020 08.
Article in English | MEDLINE | ID: covidwho-741319

ABSTRACT

Coronavirus disease 2019 caused by SARS-CoV-2 originated from China and spread across every corner of the world. The scientific interest on COVID-19 increased after WHO declared it a pandemic in the early February of 2020. In fact, this pandemic has had a worldwide impact on economy, health, and lifestyle like no other in the last 100 years. SARS-CoV-2 belongs to Coronaviridae family and causes the deadliest clinical manifestations when compared to other viruses in the family. COVID-19 is an emerging zoonotic disease that has resulted in over 383,000 deaths around the world. Scientists are scrambling for ideas to develop treatment and prevention strategies to thwart the disease condition. In this review, we have attempted to summarize the latest information on the virus, disease, prevention, and treatment strategies. The future looks promising.


Subject(s)
Betacoronavirus/pathogenicity , Communicable Disease Control/organization & administration , Coronavirus Infections/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Antiviral Agents/therapeutic use , Ataxia/diagnosis , Ataxia/physiopathology , Ataxia/virology , Communicable Disease Control/methods , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Coronavirus Infections/transmission , Humans , Hydroxychloroquine/therapeutic use , Nausea/diagnosis , Nausea/physiopathology , Nausea/virology , Pandemics/prevention & control , Personal Protective Equipment/supply & distribution , Pneumonia, Viral/prevention & control , Pneumonia, Viral/therapy , Pneumonia, Viral/transmission , Quarantine/methods , Quarantine/organization & administration , Risk Factors , Severity of Illness Index , Social Distance , Vomiting/diagnosis , Vomiting/physiopathology , Vomiting/virology
6.
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 , 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 , Spinal Cord Ischemia/prevention & control , Vertebral Artery/surgery
7.
Trials ; 21(1): 754, 2020 Aug 31.
Article in English | MEDLINE | ID: covidwho-736432

ABSTRACT

OBJECTIVES: To evaluate the effect of the combination of hydroxychloroquine (HCQ) and standard personal protective equipment (PPE) compared to the use of standard personal protective equipment alone on the proportion of laboratory confirmed COVID-19 infections among frontline healthcare workers(HCWs) in India TRIAL DESIGN: HOPE is an investigator initiated multi-centre open-label parallel group randomized controlled trial. PARTICIPANTS: All HCWs currently working in an environment with direct exposure to patients with confirmed COVID-19 infection are eligible to participate in the trial. The trial aims to be conducted across 20-30 centres (public and private hospitals) in India. HCWs who decline consent, who have a confirmed COVID-19 infection, those who are already on chloroquine/HCQ for any indication, or if pregnant or breast-feeding, or have known QT prolongation or are on medications that when taken with HCQ can prolong the QTc will be excluded. INTERVENTION AND COMPARATOR: The interventions to be compared in this trial are standard practice (use of recommended PPE) and HCQ plus standard practice. In the standard practice arm, HCWs will use recommended PPE as per institutional guidelines and based on their roles. They will be discouraged from taking HCQ to prevent contamination and contacted every week for the duration of the study to ascertain if they have taken any HCQ. Any such use will be reported as a protocol violation. In the intervention arm, HCWs will be administered 800mg of HCQ as a loading dose on the day of randomization (as two 400mg doses 12hrs apart) and subsequently continued on 400mg once a week for 12 weeks. This will be in addition to the use of recommended PPE as per institutional guidelines and based on their roles. HCWs will collect the drug once every week from designated research and pharmacy staff at site. A weekly phone reminder will be provided to participants in this arm to ensure compliance. An ECG will be performed between 4-6 weeks in this arm and if the QTc is prolonged (greater than 450milliseconds), the drug will be stopped. Follow-up will however continue. Participants in both arms will receive a weekly phone call for evaluation of the primary outcome, to monitor protocol compliance and development of any adverse events (in the HCQ group). MAIN OUTCOMES: Participants will be followed on a weekly basis. The primary outcome is the proportion of HCWs developing laboratory confirmed COVID-19 infection within 6 months of randomization. We will also evaluate a number of secondary outcomes, including hospitalization related to suspected/confirmed COVID-19 infection, intensive care unit or high-dependency unit admission due to suspected/confirmed COVID-19 infection, all-cause mortality, need for organ support ( non-invasive or invasive ventilation, vasopressors and renal replacement therapy), ICU and hospital length of stay, readmission, days off work and treatment-related adverse events. RANDOMISATION: Randomisation will be conducted through a password-protected, secure website using a central, computer-based randomisation program. Randomisation will be stratified by participating institutions and by the role of HCW - nursing, medical and other. Participants will be randomised 1:1 to either standard practice only or HCQ plus standard practice. Allocation concealment is maintained by central web-based randomisation BLINDING (MASKING): This is an unblinded study: study assigned treatment will be known to the research team and participant. Bias will be mitigated through an objective end point (laboratory confirmed COVID-19 infection). NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 6,950 HCWs will be enrolled (3475 to the intervention) and (3475 to the standard practice group) to detect a 25% relative reduction, or 2.5% absolute reduction, in the infection rate from an estimated baseline infection rate of 10%, with 80% statistical power using a two-sided test at 5% level of significance. Available data from China and Italy indicate that the rate of infection among frontline healthcare workers varies between 4% to 12%. We therefore assumed a baseline infection rate of 10% among HCWs. This sample size allows for a potential loss to follow-up rate of 10% and a potential non-compliance rate of 10% in both the treatment and control arms. TRIAL STATUS: HOPE protocol version 3.0 dated June 3rd 2020. Recruitment started on 29th June 2020 and currently 56 participants have been enrolled. Planned completion of enrolment is January 31st 2021. TRIAL REGISTRATION: Clinical Trials Registry of India: CTRI/2020/05/025067 (prospectively registered) Date of registration: 6th May 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expedited dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Subject(s)
Coronavirus Infections/prevention & control , Enzyme Inhibitors/therapeutic use , Health Personnel , Hydroxychloroquine/therapeutic use , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Occupational Diseases/prevention & control , Pandemics/prevention & control , Personal Protective Equipment , Pneumonia, Viral/prevention & control , Betacoronavirus , Chemoprevention , Coronavirus Infections/transmission , Humans , India , Pneumonia, Viral/transmission
9.
BMJ Open Respir Res ; 7(1)2020 08.
Article in English | MEDLINE | ID: covidwho-733150

ABSTRACT

Invasive mechanical has been associated with high mortality in COVID-19. Alternative therapy of high flow nasal therapy (HFNT) has been greatly debated around the world for use in COVID-19 pandemic due to concern for increased healthcare worker transmission.This was a retrospective analysis of consecutive patients admitted to Temple University Hospital in Philadelphia, Pennsylvania, from 10 March 2020 to 24 April 2020 with moderate-to-severe respiratory failure treated with HFNT. Primary outcome was prevention of intubation. Of the 445 patients with COVID-19, 104 met our inclusion criteria. The average age was 60.66 (+13.50) years, 49 (47.12 %) were female, 53 (50.96%) were African-American, 23 (22.12%) Hispanic. Forty-three patients (43.43%) were smokers. Saturation to fraction ratio and chest X-ray scores had a statistically significant improvement from day 1 to day 7. 67 of 104 (64.42%) were able to avoid invasive mechanical ventilation in our cohort. Incidence of hospital-associated/ventilator-associated pneumonia was 2.9%. Overall, mortality was 14.44% (n=15) in our cohort with 13 (34.4%) in the progressed to intubation group and 2 (2.9%) in the non-intubation group. Mortality and incidence of pneumonia was statistically higher in the progressed to intubation group. CONCLUSION: HFNT use is associated with a reduction in the rate of invasive mechanical ventilation and overall mortality in patients with COVID-19 infection.


Subject(s)
Coronavirus Infections/therapy , Healthcare-Associated Pneumonia/epidemiology , Hypoxia/therapy , Intubation, Intratracheal/statistics & numerical data , Oxygen Inhalation Therapy/methods , Pneumonia, Viral/therapy , Respiratory Insufficiency/therapy , Adrenal Cortex Hormones/therapeutic use , African Americans , Aged , Anti-Bacterial Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antirheumatic Agents/therapeutic use , Azithromycin/therapeutic use , Betacoronavirus , Cannula , Comorbidity , Coronavirus Infections/epidemiology , Diabetes Mellitus/epidemiology , European Continental Ancestry Group , Female , Heart Diseases/epidemiology , Hispanic Americans , Humans , Hydroxychloroquine/therapeutic use , Hypertension/epidemiology , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Lung Diseases/epidemiology , Male , Middle Aged , Pandemics , Philadelphia/epidemiology , Pneumonia, Ventilator-Associated/epidemiology , Pneumonia, Viral/epidemiology , Pulse Therapy, Drug , Renal Insufficiency, Chronic/epidemiology , Retrospective Studies , Severity of Illness Index , Smoking/epidemiology
10.
Trials ; 21(1): 748, 2020 Aug 27.
Article in English | MEDLINE | ID: covidwho-733027

ABSTRACT

BACKGROUND: The first case of a coronavirus 2019 (COVID-19) infection in a Sri Lankan was reported on March 11, 2020. The situation in Sri Lanka changed with the rapid increase of personnel contracting COVID-19 in a naval base camp that housed more than 4000 people. This provided a unique opportunity to study the effectiveness of hydroxychloroquine (HCQ) for post-exposure prophylaxis (PEP), while taking stringent, non-pharmacologic, public health measures to prevent spread. Our aim is to study the effectiveness and safety of HCQ for PEP among naval personnel with exposure to COVID-19-positive patients. METHODS/DESIGN: This is a placebo-controlled, randomized, clinical trial carried out in the naval base camp and quarantine centers of the Sri Lanka Navy, Ministry of Defense, Sri Lanka. Navy personnel who are exposed to a patient with confirmed COVID-19 infection but test negative for the virus on reverse real-time polymerase chain reaction (rRT-PCR) at recruitment will be randomized, 200 to each arm, to receive HCQ or placebo and monitored for the development of symptoms or rRT-PCR positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus for 14 days. DISCUSSION: This trial will provide high-quality evidence of the effectiveness and safety of HCQ as PEP for COVID-19. The study design is unique due to the circumstances of the outbreak in a confined area among otherwise healthy adults, at a relatively early stage of its spread. TRIAL REGISTRATION: Sri Lanka Clinical Trials Registry (SLCTR) SLCTR/2020/011 . Registered on 04 May 2020.


Subject(s)
Coronavirus Infections/prevention & control , Enzyme Inhibitors/therapeutic use , Hydroxychloroquine/therapeutic use , Military Personnel , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Post-Exposure Prophylaxis/methods , Betacoronavirus , Double-Blind Method , Humans , Sri Lanka
11.
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
12.
Med Oncol ; 37(10): 86, 2020 Aug 24.
Article in English | MEDLINE | ID: covidwho-728270

ABSTRACT

The COVID-19 pandemic is a kind of global disaster caused by the new coronavirus-19, the SARS-CoV-2 virus. Since the first eruption of this pandemic, which adversely affected the world in many ways, a large number of publications have been presented to the world of science. In this article, possible publication ethical dilemmas related to scientific articles increasing in number during the COVID-19 pandemic were tried to be reminded through two examples of articles.


Subject(s)
Betacoronavirus , Pandemics/ethics , Periodicals as Topic/ethics , Publication Bias , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/mortality , Coronavirus Infections/drug therapy , Coronavirus Infections/mortality , Humans , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Pneumonia, Viral/mortality
13.
Open Heart ; 7(2)2020 08.
Article in English | MEDLINE | ID: covidwho-725618

ABSTRACT

The outbreak of COVID-19 in Wuhan, China and its declaration as a global pandemic by WHO has left the medical community under significant pressure to rapidly identify effective therapeutic and preventative strategies. Chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) were found to be efficacious against SARS-CoV-2 when investigated in preliminary in vitro experiments. Reports of success in early clinical studies were widely publicised by news outlets, politicians and on social media. These results led several countries to approve the use of these drugs for the treatment of patients with COVID-19. Despite having reasonable safety profiles in the treatment of malaria and certain autoimmune conditions, both drugs are known to have potential cardiotoxic side effects. There is a high incidence of myocardial injury and arrhythmia reported with COVID-19 infection, and as such this population may be more susceptible to this side-effect profile. Studies to date have now demonstrated that in patients with COVID-19, these drugs are associated with significant QTc prolongation, as well as reports of ventricular arrhythmias. Furthermore, subsequent studies have failed to demonstrate clinical benefit from either drug. Indeed, clinical trials have also been stopped early due to safety concerns over HCQ. There is an urgent need for credible solutions to the global pandemic, but we argue that in the absence of high-quality evidence, there needs to be greater caution over the routine use or authorisation of drugs for which efficacy and safety is unproven.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Electrocardiography/drug effects , Long QT Syndrome/chemically induced , Pneumonia, Viral/drug therapy , Risk Assessment , Antimalarials/adverse effects , Antimalarials/therapeutic use , Coronavirus Infections/epidemiology , Global Health , Humans , Hydroxychloroquine/adverse effects , Hydroxychloroquine/therapeutic use , Incidence , Long QT Syndrome/physiopathology , Pandemics , Pneumonia, Viral/epidemiology
14.
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 , 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 , Treatment Outcome
15.
PLoS One ; 15(8): e0237903, 2020.
Article in English | MEDLINE | ID: covidwho-724760

ABSTRACT

AIM: To identify investigated interventions for COVID-19 prevention or treatment via trial registry entries on planned or ongoing randomised clinical trials. To assess these registry entries for recruitment status, planned trial size, blinding and reporting of mortality. METHODS: We identified trial registry entries systematically via the WHO International Clinical Trials Registry Platform and 33 trial registries up to June 23, 2020. We included relevant trial registry entries for randomized clinical trials investigating medical preventive, adjunct or supportive therapies and therapeutics for treatment of COVID-19. Studies with non-random and single-arm design were excluded. Trial registry entries were screened by two authors independently and data were systematically extracted. RESULTS: We included 1303 trial registry entries from 71 countries investigating 381 different single interventions. Blinding was planned in 47% of trials. Sample size was >200 participants in 40% of trials and a total of 611,364 participants were planned for inclusion. Mortality was listed as an outcome in 57% of trials. Recruitment was ongoing in 54% of trials and completed in 8%. Thirty-five percent were multicenter trials. The five most frequent investigational categories were immune modulating drugs (266 trials (20%)), unconventional medicine (167 trials (13%)), antimalarial drugs (118 trials (9%)), antiviral drugs (100 trials (8%)) and respiratory adjuncts (78 trials (6%)). The five most frequently tested uni-modal interventions were: chloroquine/hydroxychloroquine (113 trials with 199,841 participants); convalescent plasma (64 trials with 11,840 participants); stem cells (51 trials with 3,370 participants); tocilizumab (19 trials with 4,139 participants) and favipiravir (19 trials with 3,210 participants). CONCLUSION: An extraordinary number of randomized clinical trials investigating COVID-19 management have been initiated with a multitude of medical preventive, adjunctive and treatment modalities. Blinding will be used in only 47% of trials, which may have influence on future reported treatment effects. Fifty-seven percent of all trials will assess mortality as an outcome facilitating future meta-analyses.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/drug therapy , Pneumonia, Viral/prevention & control , Randomized Controlled Trials as Topic , Registries , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antimalarials/therapeutic use , Antiviral Agents/therapeutic use , Coronavirus Infections/mortality , Coronavirus Infections/virology , Drug Therapy, Combination , Humans , Hydroxychloroquine/therapeutic use , Interleukin-6/antagonists & inhibitors , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Treatment Outcome
16.
J Med Internet Res ; 22(8): e20007, 2020 08 17.
Article in English | MEDLINE | ID: covidwho-721428

ABSTRACT

BACKGROUND: Rapid access to evidence is crucial in times of an evolving clinical crisis. To that end, we propose a novel approach to answer clinical queries, termed rapid meta-analysis (RMA). Unlike traditional meta-analysis, RMA balances a quick time to production with reasonable data quality assurances, leveraging artificial intelligence (AI) to strike this balance. OBJECTIVE: We aimed to evaluate whether RMA can generate meaningful clinical insights, but crucially, in a much faster processing time than traditional meta-analysis, using a relevant, real-world example. METHODS: The development of our RMA approach was motivated by a currently relevant clinical question: is ocular toxicity and vision compromise a side effect of hydroxychloroquine therapy? At the time of designing this study, hydroxychloroquine was a leading candidate in the treatment of coronavirus disease (COVID-19). We then leveraged AI to pull and screen articles, automatically extract their results, review the studies, and analyze the data with standard statistical methods. RESULTS: By combining AI with human analysis in our RMA, we generated a meaningful, clinical result in less than 30 minutes. The RMA identified 11 studies considering ocular toxicity as a side effect of hydroxychloroquine and estimated the incidence to be 3.4% (95% CI 1.11%-9.96%). The heterogeneity across individual study findings was high, which should be taken into account in interpretation of the result. CONCLUSIONS: We demonstrate that a novel approach to meta-analysis using AI can generate meaningful clinical insights in a much shorter time period than traditional meta-analysis.


Subject(s)
Artificial Intelligence , Coronavirus Infections/drug therapy , Eye Diseases/etiology , Hydroxychloroquine/adverse effects , Hydroxychloroquine/therapeutic use , Meta-Analysis as Topic , Pneumonia, Viral/drug therapy , Eye/drug effects , Eye/pathology , Humans , Pandemics , Time Factors
18.
Trials ; 21(1): 702, 2020 Aug 08.
Article in English | MEDLINE | ID: covidwho-717541

ABSTRACT

OBJECTIVES: To evaluate the effectiveness of Hydroxychloroquine Phosphate/Sulfate (200 mg orally 8 hourly thrice a day for 5 days), versus oseltamivir (75 mg orally twice a day for 5 days), and versus Azithromycin (500 mg orally daily on day 1, followed by 250 mg orally twice a day on days 2-5) alone and in combination (in all seven groups), in clearing the coronavirus (COVID-19) nucleic acid from throat and nasal swab and in bringing about clinical improvement on day 7 of follow-up (primary outcomes). TRIAL DESIGN: An adaptive design, set within a comprehensive cohort study, to permit flexibility in this fast-changing clinical and public health scenario. The randomized study will be a multicenter, multiarm, multistage, randomized controlled trial with a parallel design. An observation only cohort will emerge from those not consenting to randomization. PARTICIPANTS: Eligible will be newly diagnosed patients, either hospitalized or in self-isolation, without any comorbidities or with controlled chronic medical conditions like diabetes mellitus and hypertension. Participants of any gender or age group having tested positive for COVID-19 on Real-Time qRT-PCR (Quantitative Reverse Transcription PCR) will be invited to take part in study at twelve centers across eight cities in Pakistan. Those pregnant or lactating, severely dyspneic or with respiratory distress, already undergoing treatment, and with serious comorbidities like liver or kidney failure will be excluded. INTERVENTION AND COMPARATOR: There will be a total of seven comparator groups: Each drug (Hydroxychloroquine Phosphate/Sulfate, Oseltamivir and Azithromycin) given as monotherapy (three groups); combinations of each of two drugs (three groups); and a final group on triple drug regimen. MAIN OUTCOMES: The laboratory-based primary outcome will be turning the test negative for COVID-19 on qRT-PCR on day 7 of follow-up. The clinical primary outcome will be improvement from baseline of two points on a seven-category ordinal scale of clinical status on day 7 of follow-up. RANDOMIZATION: Participants will be randomized, maintaining concealment of allocation sequence, using a computer-generated random number list of variable block size into multiple intervention groups in the allocation ratio of 1:1 for all groups. BLINDING (MASKING): This is an open label study, neither physician nor participants will be blinded. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): This is an adaptive design and parameters for formal sample size calculation in a new disease of a previously unknown virus are not available. Thus, the final sample size will be subjected to periodic reviews at each stage of adaptive design and subsequent advice of National Data Safety & Management Board (NDSMB) notified by Drug Regulatory Authority of Pakistan. TRIAL STATUS: Protocol Version 1.7 dated July 5, 2020. By July 03, 2020, the trial had recruited a total of about 470 participants across 12 centers after approval from the National Bioethics Committee and Drug Regulatory Authority of Pakistan. Recruitment started on April 20, 2020. The recruitment is expected to continue for at least three months subject to review by the National Data Safety and Management Board (NDSMB) notified by Drug Regulatory Authority of Pakistan. TRIAL REGISTRATION: Prospectively registered on 8 April 2020 at clinicaltrials.gov ID: NCT04338698 The full protocol is attached as an additional file, accessible from the Trials website (Additional file1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file2).


Subject(s)
Azithromycin/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Hydroxychloroquine/therapeutic use , Oseltamivir/therapeutic use , Pneumonia, Viral/drug therapy , Randomized Controlled Trials as Topic , Comorbidity , Humans , Pandemics , Research Design
19.
Clin Ther ; 42(6): 962-963, 2020 06.
Article in English | MEDLINE | ID: covidwho-716622

ABSTRACT

The COVID-19 pandemic embodies overwhelming stresses-unemployment, death, and isolation, among others. When called upon, clinicians must try to sort out demoralization from depression. This commentary discerns the characteristics of demoralization versus depression, and suggests solutions for both, together with a cautionary word on the use chloroquine and hydroxychloroquine in patients with COVID-19.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/epidemiology , Coronavirus Infections/psychology , Depression/diagnosis , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/psychology , Anxiety/diagnosis , Anxiety/psychology , Chloroquine/therapeutic use , Coronavirus Infections/drug therapy , Depression/psychology , Humans , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Unemployment/psychology
20.
J Med Internet Res ; 22(9): e21758, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-714139

ABSTRACT

BACKGROUND: During the initial phases of the COVID-19 pandemic, there was an unfounded fervor surrounding the use of hydroxychloroquine (HCQ) and tocilizumab (TCZ); however, evidence on their efficacy and safety have been controversial. OBJECTIVE: The purpose of this study is to evaluate the overall clinical effectiveness of HCQ and TCZ in patients with COVID-19. We hypothesize that HCQ and TCZ use in these patients will be associated with a reduction in in-hospital mortality, upgrade to intensive medical care, invasive mechanical ventilation, or acute renal failure needing dialysis. METHODS: A retrospective cohort study was performed to determine the impact of HCQ and TCZ use on hard clinical outcomes during hospitalization. A total of 176 hospitalized patients with a confirmed COVID-19 diagnosis was included. Patients were divided into two comparison groups: (1) HCQ (n=144) vs no-HCQ (n=32) and (2) TCZ (n=32) vs no-TCZ (n=144). The mean age, baseline comorbidities, and other medications used during hospitalization were uniformly distributed among all the groups. Independent t tests and multivariate logistic regression analysis were performed to calculate mean differences and adjusted odds ratios with 95% CIs, respectively. RESULTS: The unadjusted odds ratio for patients upgraded to a higher level of care (ie, intensive care unit) (OR 2.6, 95% CI 1.19-5.69; P=.003) and reductions in C-reactive protein (CRP) level on day 7 of hospitalization (21% vs 56%, OR 0.21, 95% CI 0.08-0.55; P=.002) were significantly higher in the TCZ group compared to the control group. There was no significant difference in the odds of in-hospital mortality, upgrade to intensive medical care, need for invasive mechanical ventilation, acute kidney failure necessitating dialysis, or discharge from the hospital after recovery in both the HCQ and TCZ groups compared to their respective control groups. Adjusted odds ratios controlled for baseline comorbidities and medications closely followed the unadjusted estimates. CONCLUSIONS: In this cohort of patients with COVID-19, neither HCQ nor TCZ offered a significant reduction in in-hospital mortality, upgrade to intensive medical care, invasive mechanical ventilation, or acute renal failure needing dialysis. These results are similar to the recently published preliminary results of the HCQ arm of the Recovery trial, which showed no clinical benefit from the use of HCQ in hospitalized patients with COVID-19 (the TCZ arm is ongoing). Double-blinded randomized controlled trials are needed to further evaluate the impact of these drugs in larger patient samples so that data-driven guidelines can be deduced to combat this global pandemic.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Coronavirus Infections/drug therapy , Coronavirus Infections/mortality , Hospital Mortality , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Pneumonia, Viral/mortality , Aged , Antibodies, Monoclonal, Humanized/pharmacology , Female , Hospitalization/statistics & numerical data , Humans , Hydroxychloroquine/adverse effects , Hydroxychloroquine/pharmacology , Male , Middle Aged , Odds Ratio , Pandemics , Retrospective Studies , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL