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2.
Int J Infect Dis ; 108: 45-52, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1409643

ABSTRACT

OBJECTIVES: The overall death toll from COVID-19 in Africa is reported to be low but there is little individual-level evidence on the severity of the disease. This study examined the clinical spectrum and outcome of patients monitored in COVID-19 care centres (CCCs) in two West-African countries. METHODS: Burkina Faso and Guinea set up referral CCCs to hospitalise all symptomatic SARS-CoV-2 carriers, regardless of the severity of their symptoms. Data collected from hospitalised patients by November 2020 are presented. RESULT: A total of 1,805 patients (64% men, median age 41 years) were admitted with COVID-19. Symptoms lasted for a median of 7 days (IQR 4-11). During hospitalisation, 443 (25%) had a SpO2 < 94% at least once, 237 (13%) received oxygen and 266 (15%) took corticosteroids. Mortality was 5% overall, and 1%, 5% and 14% in patients aged <40, 40-59 and ≥60 years, respectively. In multivariable analysis, the risk of death was higher in men (aOR 2.0, 95% CI 1.1; 3.6), people aged ≥60 years (aOR 2.9, 95% CI 1.7; 4.8) and those with chronic hypertension (aOR 2.1, 95% CI 1.2; 3.4). CONCLUSION: COVID-19 is as severe in Africa as elsewhere, and there must be more vigilance for common risk factors such as older age and hypertension.


Subject(s)
COVID-19 , Adult , Aged , Burkina Faso/epidemiology , Female , Hospitalization , Humans , Male , Prospective Studies , Referral and Consultation , SARS-CoV-2
3.
Antiviral Res ; 193: 105137, 2021 09.
Article in English | MEDLINE | ID: covidwho-1306846

ABSTRACT

Following the emergence of SARS-CoV-2, the search for an effective and rapidly available treatment was initiated worldwide based on repurposing of available drugs. Previous reports described the antiviral activity of certain tyrosine kinase inhibitors (TKIs) targeting the Abelson kinase 2 against pathogenic coronaviruses. Imatinib, one of them, has more than twenty years of safe utilization for the treatment of hematological malignancies. In this context, Imatinib was rapidly evaluated in clinical trials against Covid-19. Here, we present the pre-clinical evaluation of imatinib in multiple models. Our results indicated that imatinib and another TKI, the masitinib, exhibit an antiviral activity in VeroE6 cells. However, imatinib was inactive in a reconstructed bronchial human airway epithelium model. In vivo, imatinib therapy failed to impair SARS-CoV-2 replication in a golden Syrian hamster model despite high concentrations in plasma and in the lung. Overall, these results do not support the use of imatinib and similar TKIs as antivirals in the treatment of Covid-19.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Imatinib Mesylate/pharmacology , SARS-CoV-2/drug effects , Animals , COVID-19/epidemiology , COVID-19/virology , Cell Line , Chlorocebus aethiops , Drug Evaluation, Preclinical , Drug Repositioning , Enzyme Inhibitors/pharmacology , Epithelium , Female , Humans , Lung/pathology , Male , Mesocricetus , Vero Cells , Virus Replication/drug effects
4.
J Clin Virol ; 141: 104878, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1253161

ABSTRACT

OBJECTIVE: There is a lack of data evaluating performance of antigenic test (AT) for SARS-CoV-2 diagnosis (Ag-RDT) in clinical practice, especially in asymptomatic subjects. The main objective of this study was to evaluate the diagnostic performance of AT compared to Reverse Transcription Polymerase Chain Reaction (RT-PCR) for SARS-CoV-2 diagnosis. METHODS: StudyCov is a monocentric cross-sectional study. A SARS-CoV-2 screening facility was set up in the Bordeaux University health campus from October 28th to November 20th 2020. Students willing to have a RT-PCR test (ARGENE SARS-CoV-2 R-GENE, BioMérieux, France) for SARS-CoV-2 diagnosis were also offered the Abbott Panbio™ SARS-CoV-2 antigenic rapid test. All participants attending the screening facility with an AT in addition to RT-PCR and having signed an informed consent were included in the study. The main objective was to assess performance of AT as compared with RT-PCR in the recruited population. Secondary objectives dealt with the analysis of the main objective stratified by current symptoms and risk exposure. A sensitivity analysis with different RT-PCR cycle thresholds was included. RESULTS: RT-PCR and AT results were available for 692 subjects. Overall sensitivity and specificity of AT tests were respectively 63.5% (95% confidence interval (CI): 49.0 - 76.4) and 100% (95% CI: 99.4 - 100). In the asymptomatic sub-group, they were respectively 35.0% (95% CI: 15.4% - 59.2%) and 100% (95% CI: 99.3 - 100). CONCLUSIONS: This study shows the poor sensitivity of AT in asymptomatic subjects, specificity being however excellent. The performance results fall below the World Health Organization recommendation of 80% sensitivity and question using AT in general population, especially when asymptomatic.


Subject(s)
COVID-19 , COVID-19 Testing , Cross-Sectional Studies , Humans , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Sensitivity and Specificity , Students
7.
Trials ; 21(1): 846, 2020 Oct 13.
Article in English | MEDLINE | ID: covidwho-868572

ABSTRACT

OBJECTIVES: To assess the efficacy of several repurposed drugs to prevent hospitalisation or death in patients aged 65 or more with recent symptomatic SARS-CoV-2 infection (COVID-19) and no criteria for hospitalisation. TRIAL DESIGN: Phase III, multi-arm (5) and multi-stage (MAMS), randomized, open-label controlled superiority trial. Participants will be randomly allocated 1:1:1:1:1 to the following strategies: Arm 1: Control arm Arms 2 to 5: Experimental treatment arms Planned interim analyses will be conducted at regular intervals. Their results will be reviewed by an Independent Data and Safety Monitoring Board. Experimental arms may be terminated for futility, efficacy or toxicity before the end of the trial. New experimental arms may be added if new evidence suggests that other treatments should be tested. A feasibility and acceptability substudy as well as an immunological substudy will be conducted alongside the trial. PARTICIPANTS: Inclusion criteria are: 65-year-old or more; Positive test for SARS-CoV-2 on a nasopharyngeal swab; Symptoms onset within 3 days before diagnosis; No hospitalisation criteria; Signed informed consent; Health insurance. Exclusion criteria are: Inability to make an informed decision to participate (e.g.: dementia, guardianship); Rockwood Clinical Frailty Scale ≥7; Long QT syndrome; QTc interval > 500 ms; Heart rate <50/min; Kalaemia >5.5 mmol/L or <3.5 mmol/L; Ongoing treatment with piperaquine, halofantrine, dasatinib, nilotinib, hydroxyzine, domperidone, citalopram, escitalopram, potent inhibitors or inducers of cytochrome P450 CYP3A4 isoenzyme, repaglinide, azathioprine, 6-mercaptopurine, theophylline, pyrazinamide, warfarin; Known hypersensitivity to any of the trial drugs or to chloroquine and other 4-aminoquinolines, amodiaquine, mefloquine, glafenine, floctafenine, antrafenine, ARB; Hepatic porphyria; Liver failure (Child-Pugh stage ≥B); Stage 4 or 5 chronic kidney disease (GFR <30 mL/min/1.73 m²); Dialysis; Hypersentivity to lactose; Lactase deficiency; Abnormalities in galactose metabolism; Malabsorption syndrome; Glucose-6-phosphate dehydrogenase deficiency; Symptomatic hyperuricemia; Ileus; Colitis; Enterocolitis; Chronic hepatitis B virus disease. The trial is being conducted in France in the Bordeaux, Corse, Dijon, Nancy, Paris and Toulouse areas as well as in the Grand Duchy of Luxembourg. Participants are recruited either at home, nursing homes, general practices, primary care centres or hospital outpatient consultations. INTERVENTION AND COMPARATOR: The four experimental treatments planned in protocol version 1.2 (April 8th, 2020) are: (1) Hydroxychloroquine 200 mg, 2 tablets BID on day 0, 2 tablets QD from day 1 to 9; (2) Imatinib 400 mg, 1 tablet QD from day 0 to 9; (3) Favipiravir 200 mg, 12 tablets BID on day 0, 6 tablets BID from day 1 to 9; (4) Telmisartan 20 mg, 1 tablet QD from day 0 to 9. The comparator is a complex of vitamins and trace elements (AZINC Forme et Vitalité®), 1 capsule BID for 10 days, for which there is no reason to believe that they are active on the virus. In protocol version 1.2 (April 8th, 2020): People in the control arm will receive a combination of vitamins and trace elements; people in the experimental arms will receive hydroxychloroquine, or favipiravir, or imatinib, or telmisartan. MAIN OUTCOME: The primary outcome is the proportion of participants with an incidence of hospitalisation and/or death between inclusion and day 14 in each arm. RANDOMISATION: Participants are randomized in a 1:1:1:1:1 ratio to each arm using a web-based randomisation tool. Participants not treated with an ARB or ACEI prior to enrolment are randomized to receive the comparator or one of the four experimental drugs. Participants already treated with an ARB or ACEI are randomized to receive the comparator or one of the experimental drugs except telmisartan (i.e.: hydroxychloroquine, imatinib, or favipiravir). Randomisation is stratified on ACEI or ARBs treatment at inclusion and on the type of residence (personal home vs. nursing home). BLINDING (MASKING): This is an open-label trial. Participants, caregivers, investigators and statisticians are not blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 1057 participants will be enrolled if all arms are maintained until the final analysis and no additional arm is added. Three successive futility interim analyses are planned, when the number of participants reaches 30, 60 and 102 in the control arm. Two efficacy analyses (interim n°3 and final) will be performed successively. TRIAL STATUS: This describes the Version 1.2 (April 8th, 2020) of the COVERAGE protocol that was approved by the French regulatory authority and ethics committee. The trial was opened for enrolment on April 15th, 2020 in the Nouvelle Aquitaine region (South-West France). Given the current decline of the COVID-19 pandemic in France and its unforeseeable dynamic in the coming months, new trial sites in 5 other French regions and in Luxembourg are currently being opened. A revised version of the protocol was submitted to the regulatory authority and ethics committee on June 15th, 2020. It contains the following amendments: (i) Inclusion criteria: age ≥65 replaced by age ≥60; time since first symptoms <3 days replaced by time since first symptoms <5 days; (ii) Withdrawal of the hydroxychloroquine arm (due to external data); (iii) increase in the number of trial sites. TRIAL REGISTRATION: The trial was registered on Clinical Trials.gov on April 22nd, 2020 (Identifier: NCT04356495): and on EudraCT on April 10th, 2020 (Identifier: 2020-001435-27). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of 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 file 2).


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/drug therapy , Outpatients/statistics & numerical data , Pneumonia, Viral/drug therapy , Therapies, Investigational/statistics & numerical data , Aged , Aged, 80 and over , Amides/therapeutic use , Antihypertensive Agents/therapeutic use , Antimalarials/therapeutic use , Antiviral Agents/therapeutic use , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Drug Tolerance , Feasibility Studies , France/epidemiology , Hospitalization/trends , Humans , Hydroxychloroquine/therapeutic use , Imatinib Mesylate/therapeutic use , Luxembourg/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Protein Kinase Inhibitors/therapeutic use , Pyrazines/therapeutic use , Risk Reduction Behavior , SARS-CoV-2 , Telmisartan/therapeutic use , Treatment Outcome
10.
CPT Pharmacometrics Syst Pharmacol ; 9(9): 509-514, 2020 09.
Article in English | MEDLINE | ID: covidwho-603799

ABSTRACT

We modeled the viral dynamics of 13 untreated patients infected with severe acute respiratory syndrome-coronavirus 2 to infer viral growth parameters and predict the effects of antiviral treatments. In order to reduce peak viral load by more than two logs, drug efficacy needs to be > 90% if treatment is administered after symptom onset; an efficacy of 60% could be sufficient if treatment is initiated before symptom onset. Given their pharmacokinetic/pharmacodynamic properties, current investigated drugs may be in a range of 6-87% efficacy. They may help control virus if administered very early, but may not have a major effect in severely ill patients.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , SARS-CoV-2/physiology , Antiviral Agents/pharmacology , Humans , Lopinavir/pharmacology , Lopinavir/therapeutic use , Models, Theoretical , Ritonavir/pharmacology , Ritonavir/therapeutic use , SARS-CoV-2/drug effects , Severity of Illness Index , Singapore , Treatment Outcome , Viral Load/drug effects
12.
Lancet Infect Dis ; 20(6): 697-706, 2020 06.
Article in English | MEDLINE | ID: covidwho-17918

ABSTRACT

BACKGROUND: On Dec 31, 2019, China reported a cluster of cases of pneumonia in people at Wuhan, Hubei Province. The responsible pathogen is a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the relevant features of the first cases in Europe of confirmed infection, named coronavirus disease 2019 (COVID-19), with the first patient diagnosed with the disease on Jan 24, 2020. METHODS: In this case series, we followed five patients admitted to Bichat-Claude Bernard University Hospital (Paris, France) and Pellegrin University Hospital (Bordeaux, France) and diagnosed with COVID-19 by semi-quantitative RT-PCR on nasopharyngeal swabs. We assessed patterns of clinical disease and viral load from different samples (nasopharyngeal and blood, urine, and stool samples), which were obtained once daily for 3 days from hospital admission, and once every 2 or 3 days until patient discharge. All samples were refrigerated and shipped to laboratories in the National Reference Center for Respiratory Viruses (The Institut Pasteur, Paris, and Hospices Civils de Lyon, Lyon, France), where RNA extraction, real-time RT-PCR, and virus isolation and titration procedures were done. FINDINGS: The patients were three men (aged 31 years, 48 years, and 80 years) and two women (aged 30 years and 46 years), all of Chinese origin, who had travelled to France from China around mid-January, 2020. Three different clinical evolutions are described: (1) two paucisymptomatic women diagnosed within a day of exhibiting symptoms, with high nasopharyngeal titres of SARS-CoV-2 within the first 24 h of the illness onset (5·2 and 7·4 log10 copies per 1000 cells, respectively) and viral RNA detection in stools; (2) a two-step disease progression in two young men, with a secondary worsening around 10 days after disease onset despite a decreasing viral load in nasopharyngeal samples; and (3) an 80-year-old man with a rapid evolution towards multiple organ failure and a persistent high viral load in lower and upper respiratory tract with systemic virus dissemination and virus detection in plasma. The 80-year-old patient died on day 14 of illness (Feb 14, 2020); all other patients had recovered and been discharged by Feb 19, 2020. INTERPRETATION: We illustrated three different clinical and biological types of evolution in five patients infected with SARS-CoV-2 with detailed and comprehensive viral sampling strategy. We believe that these findings will contribute to a better understanding of the natural history of the disease and will contribute to advances in the implementation of more efficient infection control strategies. FUNDING: REACTing (Research & Action Emerging Infectious Diseases).


Subject(s)
Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Adult , Aged, 80 and over , Betacoronavirus/isolation & purification , Blood/virology , COVID-19 , China , Coronavirus Infections/virology , Feces/virology , Female , France/epidemiology , Humans , Male , Middle Aged , Nasopharynx/virology , Pandemics , Pneumonia, Viral/virology , RNA, Viral/isolation & purification , SARS-CoV-2 , Travel , Urine/virology , Viral Load
13.
Euro Surveill ; 25(6)2020 02.
Article in English | MEDLINE | ID: covidwho-868

ABSTRACT

A novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) causing a cluster of respiratory infections (coronavirus disease 2019, COVID-19) in Wuhan, China, was identified on 7 January 2020. The epidemic quickly disseminated from Wuhan and as at 12 February 2020, 45,179 cases have been confirmed in 25 countries, including 1,116 deaths. Strengthened surveillance was implemented in France on 10 January 2020 in order to identify imported cases early and prevent secondary transmission. Three categories of risk exposure and follow-up procedure were defined for contacts. Three cases of COVID-19 were confirmed on 24 January, the first cases in Europe. Contact tracing was immediately initiated. Five contacts were evaluated as at low risk of exposure and 18 at moderate/high risk. As at 12 February 2020, two cases have been discharged and the third one remains symptomatic with a persistent cough, and no secondary transmission has been identified. Effective collaboration between all parties involved in the surveillance and response to emerging threats is required to detect imported cases early and to implement adequate control measures.


Subject(s)
Contact Tracing , Coronavirus Infections , Infection Control , Pneumonia, Viral , Population Surveillance , Adult , Betacoronavirus/isolation & purification , COVID-19 , China/epidemiology , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , France/epidemiology , Humans , Male , Middle Aged , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Risk Assessment , SARS-CoV-2 , Travel
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