Publications by authors named "Yazdan Yazdanpanah"

291 Publications

Assessment of HIV-postexposure prophylaxis prescription quality after a training programme and assistance in decisions provided by a computer-based decision program: a cross-over study.

Acta Clin Belg 2021 Mar 30:1-15. Epub 2021 Mar 30.

Assistance Publique-Hôpitaux De Paris (AP-HP), Hôpital Bichat, Emergency Department, Paris, France.

Among the tools for preventing HIV transmission, post-exposureprophylaxis (PEP) is an effective means after potential HIV exposure.To evaluate aPEP training program and acomputer-baseddecision program (CBDP) using simulated patients in emergency department (ED) on the quality of PEP prescriptionThis cross-overstudy, carried out from 7January2019 to 28June2019, included 20 ED physicians from 10 tertiary referral hospitals. Intervention consisted of two parts: Period Aassessed physicians' compliance with PEP prescription guidelines before and after atraining program, using 400 post-exposuremedical records (200 occupational and 200 non-occupational). Period Bconsisted of arandomized crossover study involving 40 simulated patients, with physicians using or not using aCBDP. Sensitivity, specificity, and accuracy of PEP prescription in accordance with the guidelines were assessed. In period A, alpha Cronbach was less than 0.7 whereas it increased after the training to be >0.7. Sensitivity increased, especially for occupational patients ranging from 51.8%-66.6% to 70.4%-90.1%, whereas specificity increased for non-occupationalpatients ranging from 15.5%-51.9% to 52.1%-75.3%. In period B, sensitivity, specificity, and rate of complete assessments significantly increased (p < 0.0001) after the initiation of CBDP. Rate of PEP prescription significantly decreased (p < 0.001) for all subcategories. Significant recommendations-discordantprescriptions, mainly overprescription, occurred for patients visiting ED for PEP. Training improved quality of PEP prescription but the reduction was modest. The availability of CBDP improved quality of PEP prescription and allowed for better data collection and reduction of PEP prescription.
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http://dx.doi.org/10.1080/17843286.2021.1892422DOI Listing
March 2021

COVID-19 vaccines: A race against time.

Anaesth Crit Care Pain Med 2021 Mar 24;40(2):100848. Epub 2021 Mar 24.

Department of Anaesthesiology and Critical Care Medicine, Bichat-Claude Bernard Hospital, Assistance-Publique Hôpitaux de Paris, Paris, France; Université de Paris, Paris, France; INSERM UMR1152, ANR-10-LABX-17, Paris, France.

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http://dx.doi.org/10.1016/j.accpm.2021.100848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987582PMC
March 2021

Long term SARS-CoV-2 infectiousness among three immunocompromised patients: from prolonged viral shedding to SARS-CoV-2 superinfection.

J Infect Dis 2021 Feb 8. Epub 2021 Feb 8.

Laboratoire de Virologie, Hôpital Bichat Claude Bernard, AP-HP, Paris, France.

Guidelines for stopping COVID-19 patient isolation are mainly symptom-based, with isolation for 10 to 20 days depending on their condition. Here, we describe three deeply immunocompromised patients, each with different clinical evolutions. Asymptomatic carriage, symptom resolution, or superinfection with a second SARS-CoV-2 strain were observed, all leading to prolonged infectious viral shedding several months. We followed the patients epidemiological, clinical, serological data, infectiousness using viral culture and viral mutations accumulated over time. Understanding underlying mechanisms and frequency of prolonged infectiousness is crucial to adapt current guidelines and strengthen the use of systematic PCR testing before stopping isolation in immunocompromised populations.
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http://dx.doi.org/10.1093/infdis/jiab075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928754PMC
February 2021

Arterial Thrombotic Events in Adult Inpatients With COVID-19.

Mayo Clin Proc 2021 02 27;96(2):295-303. Epub 2020 Nov 27.

Département de Médecine Interne, Hôpital Bichat, Assistance Publique Hôpitaux de Paris, Université de Paris, France; INSERM U1149, Paris, France. Electronic address:

Objective: To evaluate the clinical course of and risk factors for arterial thrombotic events in adult inpatients with coronavirus disease 2019 (COVID-19).

Methods: All consecutive adult patients admitted for COVID-19 infection in a referral center in France and discharged from the hospital between April 1 and April 30, 2020, were included. All arterial thrombotic events that occurred through discharge were considered for analysis. Epidemiologic, demographic, clinical, laboratory, treatment, and outcome data were extracted from electronic medical records with use of a standardized data collection form.

Results: Overall, 531 COVID-19+ patients were analyzed. Among them, 30 (5.6%) experienced arterial thrombotic events. Arterial thrombotic events in the setting of COVID-19 infection happened at a median of 11 (5-20) days after the first symptoms of infection; occurred in high-risk patients according to traditional cardiovascular risk factors; had an atypical pattern, such as thrombosis of the aorta, upper limb, or renal arteries or cerebral microvasculopathy in 7 (23.3%) cases; and were associated with an in-hospital mortality rate of 40%. Arterial thrombotic events increased the risk of death by 3-fold in COVID-19+ patients (hazard ratio, 2.96; 95% CI, 1.4 to 4.7; P=.002). A subdistribution survival hazard model showed that a concentration of D-dimer above 1250 ng/mL increased the risk of arterial thrombotic events in COVID-19+ patients by more than 7 (subdistribution hazard ratio, 7.68; 95% CI, 2.9 to 20.6; P<.001).

Conclusion: A dramatically high rate of in-hospital death was observed in patients who suffered arterial thrombotic events in the setting of COVID-19 infection. A D-dimer level above 1250 ng/mL at entry may identify COVID-19+ patients at risk for arterial thrombotic events.
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http://dx.doi.org/10.1016/j.mayocp.2020.11.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691140PMC
February 2021

Corrigendum to "Review of trials currently testing treatment and prevention of COVID-19" [Clin Microbiol Infect 26.8 (2020) 988-998].

Clin Microbiol Infect 2021 Mar 2;27(3):499. Epub 2021 Feb 2.

4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece; European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Respiratory Viruses (ESGREV), Switzerland. Electronic address:

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http://dx.doi.org/10.1016/j.cmi.2021.01.024DOI Listing
March 2021

Modeling SARS-CoV-2 viral kinetics and association with mortality in hospitalized patients from the French COVID cohort.

Proc Natl Acad Sci U S A 2021 02;118(8)

Université de Paris, INSERM, IAME, F-75018 Paris, France.

The characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics in hospitalized patients and its association with mortality is unknown. We analyzed death and nasopharyngeal viral kinetics in 655 hospitalized patients from the prospective French COVID cohort. The model predicted a median peak viral load that coincided with symptom onset. Patients with age ≥65 y had a smaller loss rate of infected cells, leading to a delayed median time to viral clearance occurring 16 d after symptom onset as compared to 13 d in younger patients ( < 10). In multivariate analysis, the risk factors associated with mortality were age ≥65 y, male gender, and presence of chronic pulmonary disease (hazard ratio [HR] > 2.0). Using a joint model, viral dynamics after hospital admission was an independent predictor of mortality (HR = 1.31, < 10). Finally, we used our model to simulate the effects of effective pharmacological interventions on time to viral clearance and mortality. A treatment able to reduce viral production by 90% upon hospital admission would shorten the time to viral clearance by 2.0 and 2.9 d in patients of age <65 y and ≥65 y, respectively. Assuming that the association between viral dynamics and mortality would remain similar to that observed in our population, this could translate into a reduction of mortality from 19 to 14% in patients of age ≥65 y with risk factors. Our results show that viral dynamics is associated with mortality in hospitalized patients. Strategies aiming to reduce viral load could have an effect on mortality rate in this population.
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http://dx.doi.org/10.1073/pnas.2017962118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929555PMC
February 2021

Outcome of SARS-CoV-2 infection is linked to MAIT cell activation and cytotoxicity.

Nat Immunol 2021 03 2;22(3):322-335. Epub 2021 Feb 2.

Université de Paris, Institut Cochin, Inserm U1016, Centre National de la Recherche Scientifique UMR 8104, Inflamex Laboratory, Paris, France.

Immune system dysfunction is paramount in coronavirus disease 2019 (COVID-19) severity and fatality rate. Mucosal-associated invariant T (MAIT) cells are innate-like T cells involved in mucosal immunity and protection against viral infections. Here, we studied the immune cell landscape, with emphasis on MAIT cells, in cohorts totaling 208 patients with various stages of disease. MAIT cell frequency is strongly reduced in blood. They display a strong activated and cytotoxic phenotype that is more pronounced in lungs. Blood MAIT cell alterations positively correlate with the activation of other innate cells, proinflammatory cytokines, notably interleukin (IL)-18, and with the severity and mortality of severe acute respiratory syndrome coronavirus 2 infection. We also identified a monocyte/macrophage interferon (IFN)-α-IL-18 cytokine shift and the ability of infected macrophages to induce the cytotoxicity of MAIT cells in an MR1-dependent manner. Together, our results suggest that altered MAIT cell functions due to IFN-α-IL-18 imbalance contribute to disease severity, and their therapeutic manipulation may prevent deleterious inflammation in COVID-19 aggravation.
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http://dx.doi.org/10.1038/s41590-021-00870-zDOI Listing
March 2021

Characteristics of human immunodeficiency virus exposure and predictors of time until access to postexposure prophylaxis: a prospective observational study.

Emergencias 2021 02;33(1):35-41

Head of Emergency Department, University Hospital of Bichat, París, Francia. Infection Antimicrobials Modelling Evolution (IAME) research center, UMR 1137 - INSERM. University of Paris, Faculty of Medicine Denis Diderot, París, Francia.

Objectives: The efficacy of postexposure prophylaxis (PEP) after human immunodeficiency virus (HIV) contact relies on administering the treatment within 4 hours of contact with the virus. This study aimed to evaluate predictors of the time that elapses between HIV exposure and emergency department arrival.

Material And Methods: Prospective observational study carried out at Hôpital Bichat, a university teaching hospital in Paris, France. All emergency visits for occupational or nonoccupational exposure to HIV in 2016 and 2017 were included.

Results: A total of 1475 cases were studied; 598 patients responded to the follow-up survey. A delay of 4 hours or more between HIV exposure and the emergency department visit was associated with type of contact: health care occupational exposure, other occupational exposure, or sexual intercourse (P .001). We found significant differences between individuals exposed during sexual contact versus occupational exposure with respect to knowledge of the PEP program pathway (65.2% vs 46.9%, respectively), previous use of PEP (23.9% vs 13.1%), alcohol intake (36.2% vs 18.5%), drug use (34.6% vs 8.6%), and chemsex (sexualized drug use) (26.1% vs 0%) (P .001, all comparisons). Predictors of time until start of PEP among individuals exposed during sexual intercourse were knowledge and prior use of the PEP pathway (P .001), drug use (P = .03), and chemsex (P .001). Predictors among occupationally exposed individuals were prior knowledge of the PEP pathway and drug use (P .001).

Conclusion: Delay in seeking PEP after HIV exposure is greater among individuals exposed during sexual intercourse. Knowledge of the PEP program and prior use of it are associated with less delay. Exposure during sexual intercourse, alcohol and drug use, and chemsex are associated with longer delays, especially in men who have sex with men.
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February 2021

Partnership for Research on Ebola VACcination (PREVAC): protocol of a randomized, double-blind, placebo-controlled phase 2 clinical trial evaluating three vaccine strategies against Ebola in healthy volunteers in four West African countries.

Trials 2021 Jan 23;22(1):86. Epub 2021 Jan 23.

REACTing, Institut Thématique Immunologie, Inflammation, Infectiologie et Microbiologie, Inserm, Paris, France.

Introduction: The Ebola virus disease (EVD) outbreak in 2014-2016 in West Africa was the largest on record and provided an opportunity for large clinical trials and accelerated efforts to develop an effective and safe preventative vaccine. Multiple questions regarding the safety, immunogenicity, and efficacy of EVD vaccines remain unanswered. To address these gaps in the evidence base, the Partnership for Research on Ebola Vaccines (PREVAC) trial was designed. This paper describes the design, methods, and baseline results of the PREVAC trial and discusses challenges that led to different protocol amendments.

Methods: This is a randomized, double-blind, placebo-controlled phase 2 clinical trial of three vaccine strategies against the Ebola virus in healthy volunteers 1 year of age and above. The three vaccine strategies being studied are the rVSVΔG-ZEBOV-GP vaccine, with and without a booster dose at 56 days, and the Ad26.ZEBOV,MVA-FN-Filo vaccine regimen with Ad26.ZEBOV given as the first dose and the MVA-FN-Filo vaccination given 56 days later. There have been 4 versions of the protocol with those enrolled in Version 4.0 comprising the primary analysis cohort. The primary endpoint is based on the antibody titer against the Ebola virus surface glycoprotein measured 12 months following the final injection.

Results: From April 2017 to December 2018, a total of 5002 volunteers were screened and 4789 enrolled. Participants were enrolled at 6 sites in four countries (Guinea, Liberia, Sierra Leone, and Mali). Of the 4789 participants, 2560 (53%) were adults and 2229 (47%) were children. Those < 18 years of age included 549 (12%) aged 1 to 4 years, 750 (16%) 5 to 11 years, and 930 (19%) aged 12-17 years. At baseline, the median (25th, 75th percentile) antibody titer to Ebola virus glycoprotein for 1090 participants was 72 (50, 116) EU/mL.

Discussion: The PREVAC trial is evaluating-placebo-controlled-two promising Ebola candidate vaccines in advanced stages of development. The results will address unanswered questions related to short- and long-term safety and immunogenicity for three vaccine strategies in adults and children.

Trial Registration: ClinicalTrials.gov NCT02876328 . Registered on 23 August 2016.
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http://dx.doi.org/10.1186/s13063-021-05035-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823170PMC
January 2021

Impact of mass testing during an epidemic rebound of SARS-CoV-2: a modelling study using the example of France.

Euro Surveill 2021 01;26(1)

Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, UMR2000, CNRS, Paris, France.

We used a mathematical model to evaluate the impact of mass testing in the control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Under optimistic assumptions, one round of mass testing may reduce daily infections by up to 20-30%. Consequently, very frequent testing would be required to control a quickly growing epidemic if other control measures were to be relaxed. Mass testing is most relevant when epidemic growth remains limited through a combination of interventions.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.26.1.2001978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791601PMC
January 2021

MRI Features Associated With the Detection of Microbial Pathogens by CT-Guided Biopsy in Septic Spondylodiscitis.

J Clin Rheumatol 2020 Dec 15;Publish Ahead of Print. Epub 2020 Dec 15.

From the Rheumatology Department, DHU FIRE, Pôle Infection Immunité, Bichat Hospital (AP-HP) Microbiology Department, Lariboisière Hospital, Paris Rheumatology Department, Hôtel Dieu Hospital, Nantes Rheumatology Department, Centre Viggo Petersen, Pole Appareil Locomoteur, Lariboisière Hospital (AP-HP), Inserm UMR 1132, USPC Infectious and Tropical Diseases Department, Bichat Hospital, Paris, France.

Objective: The aim of this study was to assess the magnetic resonance imaging (MRI) features associated with microbial pathogen detection by computed tomography (CT)-guided biopsy in patients with suspected septic spondylodiscitis.

Methods: For the last 10-year period, we analyzed the medical records of patients who underwent MRI and CT-guided biopsy for suspected septic spondylodiscitis. Clinical characteristics were recorded. The following MRI features were assessed: edema or contrast enhancement of the intervertebral disc, adjacent vertebrae, epidural and paravertebral space, presence of abscess, and paravertebral edema size. A positive biopsy was defined by pathogen identification on bacterial analysis or the presence of granuloma on histology. Predictors of a positive biopsy were assessed with a logistic regression model.

Results: We analyzed data for 61 patients (34 [56%] male; mean age, 59.9 ± 18.0 years); for 35 patients (57%), CT-guided biopsy was positive for a pathogen. The 4 MRI findings significantly associated with a positive biopsy were epiduritis, greater than 50% vertebral endplate edema, loss of intradiscal cleft, and abscess. The size of paravertebral edema was greater with a positive than negative biopsy (median, 15.9 [interquartile range, 11.3-21.3] vs 7.3 [4.6-12.9] mm; p = 0.004). On multivariable analysis, epiduritis was the only independent predictor of a positive biopsy (adjusted odds ratio, 7.4 [95% confidence interval, 1.7-31.4]; p = 0.006).

Conclusions: Epiduritis and the size of paravertebral edema on MRI are associated with detection of a microbial pathogen in suspected septic spondylodiscitis. For patients without these MRI signs, the need for further investigations such as enriched or prolonged cultures, a second CT-guided biopsy, or even surgical biopsy need to be discussed.
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http://dx.doi.org/10.1097/RHU.0000000000001683DOI Listing
December 2020

Detection of SARS-CoV-2 N-antigen in blood during acute COVID-19 provides a sensitive new marker and new testing alternatives.

Clin Microbiol Infect 2020 12 8. Epub 2020 Dec 8.

Université de Paris, IAME, INSERM, Paris, France; Virology, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, Paris, France. Electronic address:

Objectives: Molecular assays on nasopharyngeal swabs remain the cornerstone of COVID-19 diagnostic. The high technicalities of nasopharyngeal sampling and molecular assays, as well as scarce resources of reagents, limit our testing capabilities. Several strategies failed, to date, to fully alleviate this testing process (e.g. saliva sampling or antigen testing on nasopharyngeal samples). We assessed the clinical performances of SARS-CoV-2 nucleocapsid antigen (N-antigen) ELISA detection in serum or plasma using the COVID-19 Quantigene® (AAZ, France) assay.

Methods: Performances were determined on 63 sera from 63 non-COVID patients and 227 serum samples (165 patients) from the French COVID and CoV-CONTACT cohorts with RT-PCR confirmed SARS-CoV-2 infection, including 142 serum (114 patients) obtained within 14 days after symptoms' onset.

Results: Specificity was 98.4% (95% confidence interval [CI], 95.3 to 100). Sensitivity was 79.3% overall (180/227, 95% CI, 74.0 to 84.6) and 93.0% (132/142, 95% CI, 88.7 to 97.2) within 14 days after symptoms onset. 91 included patients had a sera and nasopharyngeal swabs collected in the same 24 hours. Among those with high nasopharyngeal viral loads, i.e. Ct value below 30 and 33, only 1/50 and 4/67 tested negative for N-antigenemia, respectively. Among those with a negative nasopharyngeal RT-PCR, 8/12 presented positive N-antigenemia; the lower respiratory tract was explored for 6 of these 8 patients, showing positive RT-PCR in 5 cases.

Conclusion: This is the first evaluation of a commercially available serum N-antigen detection assay. It presents a robust specificity and sensitivity within the first 14 days after symptoms onset. This approach provides a valuable new option for COVID-19 diagnosis, only requiring a blood draw and easily scalable in all clinical laboratories.
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http://dx.doi.org/10.1016/j.cmi.2020.11.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724284PMC
December 2020

Nebulised interferon beta-1a for patients with COVID-19.

Lancet Respir Med 2021 02 12;9(2):122-123. Epub 2020 Nov 12.

Infectious Diseases Department, Bichat-Claude Bernard Hospital, Assistance-Publique Hôpitaux de Paris, Paris, France; Université de Paris, INSERM, IAME, F-75006 Paris, France.

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http://dx.doi.org/10.1016/S2213-2600(20)30523-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833737PMC
February 2021

Impact of test-and-treat and risk reduction strategies on HCV transmission among MSM living with HIV in France: a modelling approach.

Gut 2020 Oct 27. Epub 2020 Oct 27.

Université de Paris, Inserm, IAME, F-75006 Paris, France.

Objective: Since the early 2000s, there has been an epidemic of HCV occurring among men who have sex with men (MSM) living with HIV, mainly associated with high-risk sexual and drug-related behaviours. Early HCV diagnosis and treatment, and behavioural risk-reduction, may be effective to eliminate HCV among MSM living with HIV.

Design: We developed a deterministic dynamic compartmental model to simulate the impact of test-and-treat and risk-reduction strategies on HCV epidemic (particularly on incidence and prevalence) among MSM living with HIV in France. We accounted for HIV and HCV cascades of care, HCV natural history and heterogeneity in HCV risk behaviours. The model was calibrated to primary HCV incidence observed between 2014 and 2017 among MSM living with HIV in care (ANRS CO4-French hospital database on HIV (FHDH)).

Results: With current French practices (annual HCV screening and immediate treatment), total HCV incidence would fall by 70%, from 0.82/100 person-years in 2015 to 0.24/100 person-years in 2030. It would decrease to 0.19/100 person-years in 2030 with more frequent screening and to 0.19 (0.12)/100 person-years in 2030 with a 20% (50%) risk-reduction. When combining screening every 3 months with a 50% risk-reduction, HCV incidence would be 0.11/100 person-years in 2030, allowing to get close to the WHO target (90% reduction from 2015 to 2030). Similarly, HCV prevalence would decrease from 2.79% in 2015 to 0.48% in 2030 (vs 0.71% with current practices).

Conclusion: Combining test-and-treat and risk-reduction strategies could have a marked impact on the HCV epidemic, paving the way to HCV elimination among MSM living with HIV.
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http://dx.doi.org/10.1136/gutjnl-2020-321744DOI Listing
October 2020

Comparative effectiveness of interventions to improve the HIV continuum of care and HIV Pre-Exposure Prophylaxis in Kenya: a model-based analysis.

J Infect Dis 2020 Oct 27. Epub 2020 Oct 27.

From Université de Paris, IAME, INSERM, Paris, France.

Background: In Western Kenya up to one quarter of the adult population was HIV-infected in 2012. The Ministry of Health, Médecins Sans Frontières (MSF) and partners implemented an HIV program that surpassed the 90-90-90 UNAIDS targets. In this generalized epidemic, we compared the effectiveness of Pre-exposure Prophylaxis (PrEP) with improving the continuum of care.

Methods: We developed a dynamic microsimulation model to project HIV incidence and infections averted to 2030. We modeled 3 strategies compared to a "90-90-90" continuum of care base case: 1) Scaling up the continuum of care to 95-95-95, 2) PrEP targeting young adults, with 10% coverage, and 3) Scaling up to 95-95-95 and PrEP combined.

Results: In the base case, by 2030 HIV incidence was 0.37/100 PY. Improving continuum levels to 95-95-95 averted 21.5% of infections, PrEP 8.0%, and combining 95-95-95 and PrEP 31.8%. Sensitivity analysis showed that PrEP coverage had to exceed 20% to avert as many infections as reaching 95-95-95.

Conclusions: In a generalized HIV epidemic with continuum of care levels at 90-90-90, improving the continuum to 95-95-95 is more effective than providing PrEP. Continued improvement in the continuum of care will have the greatest impact on decreasing new HIV infections.
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http://dx.doi.org/10.1093/infdis/jiaa633DOI Listing
October 2020

Impact on disease mortality of clinical, biological, and virological characteristics at hospital admission and overtime in COVID-19 patients.

J Med Virol 2021 04 10;93(4):2149-2159. Epub 2020 Nov 10.

Department of Infectious and Tropical Diseases, Bichat-Claude Bernard University Hospital, AP-HP.Nord-Université de Paris, Paris, France.

Little is known on the association between clinical factors and coronavirus disease 2019 (COVID-19) more than 15 days after diagnosis. We conducted a multicentric prospective cohort of COVID-19 hospitalized patients to describe clinical, biological, and virological characteristics at hospital admission and over time, according to mortality up to Day 60 after admission. For the analysis of risk factors of survival, analyses assessing associations between mortality and demographic characteristics or comorbidities were performed using a Cox regression model. Between January 24 and March 15, 2020, 246 patients with reverse-transcriptase polymerase chain reactions virologically confirmed COVID-19 were enrolled. In multivariate analysis, mortality at Day 60 (n = 42 patients, 17.1% [95% confidence interval, 12.6-22.4]) was associated with older age (adjusted hazard ratio [aHR] for age ≥ 65 years: 5.22 [2.56-10.63, p < .001]), gender (aHR for male: 2.97 [1.47-5.99, p = .002]), chronic pulmonary disease (aHR: 4.84 [2.32-10.07, p < .001]), obesity (aHR: 3.32 [1.70-6.52, p < .001]), and diabetes (aHR: 1.98 [1.01-3.89, p = .048]). The median nasopharyngeal viral load at admission was 6.4 log copies/ml and was associated with mortality regardless of clinical risk factors. Viral load decreased with time elapsed since symptoms onset. Our study confirmed that mortality was associated with clinical characteristics at admission. The viral load at admission was significantly lower in patients admitted late after the onset of symptoms in both dead and alive patients. Our results could improve earlier identification of patients with increased risk of mortality and adapted management.
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http://dx.doi.org/10.1002/jmv.26601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675272PMC
April 2021

Incidence and risk factors for medical care interruption in people living with HIV in a French provincial city.

PLoS One 2020 15;15(10):e0240417. Epub 2020 Oct 15.

GRAM 2.0, EA2656, UNICAEN, Normandie University Hospital, Caen, France.

Objectives: The aim of our study was to identify HIV-positive patients at risk of medical care interruption (MCI) in a provincial city of a high-income country.

Methods: We estimated the incidence rate of MCI in 989 individuals followed in an HIV clinic in Caen University Hospital, Normandy, France, between January 2010 and May 2016. We enrolled patients over 18 years old who were seen at the clinic at least twice after HIV diagnosis. Patients were considered to be in MCI if they did not attend care in or outside the clinic for at least 18 months, regardless of whether or not they came back after interruption. We investigated sociodemographic, clinical and immunovirological characteristics at HIV diagnosis and during follow-up through a Cox model analysis.

Results: The incidence rate of MCI was estimated to be 3.0 per 100 persons-years (95% confidence interval [CI] = 2.6-3.5). The independent risk factors for MCI were a linkage to care >6 months after HIV diagnosis (hazard ratio [HR] = 1.14; 95% CI = 1.08-1.21), a hepatitis C coinfection (HR = 1.76; 95% CI = 1.07-2.88), being born in Sub-Saharan Africa (HR = 2.18; 95% CI = 1.42-3.34 vs. in France) and not having a mailing address reported in the file (HR = 1.73; 95% CI = 1.07-2.80). During follow-up, the risk of MCI decreased when the patient was older (HR = 0.28; 95% CI = 0.15-0.51 when >45 vs. ≤ 30 years old) and increased when the patient was not on antiretroviral therapy (HR = 2.78; 95% CI = 1.66-4.63).

Conclusions: Our findings show that it is important to link HIV-positive individuals to care quickly after diagnosis and initiate antiretroviral therapy as soon as possible to retain them in care.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240417PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561150PMC
December 2020

COVID-19: France grapples with the pragmatics of isolation.

Lancet Public Health 2020 11 10;5(11):e573-e574. Epub 2020 Oct 10.

National Ethical Consultative Committee for Life Sciences and Health, Paris, France.

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http://dx.doi.org/10.1016/S2468-2667(20)30235-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547370PMC
November 2020

Association between renin-angiotensin-aldosterone system blockers and outcome in coronavirus disease 2019: analysing in-hospital exposure generates a biased seemingly protective effect of treatment.

J Hypertens 2021 02;39(2):367-375

Physiology Department, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital.

Objective: The role of renin-angiotensin-aldosterone system (RAAS) blockers during the coronavirus disease 2019 (COVID-19) pandemic is a matter of controversies. Studies based on in-hospital exposure have suggested a beneficial effect of these drugs, unlike those based on chronic exposure. We aimed to analyse RAAS blocker prescription before and during hospital stay in patients with COVID-19, and the corresponding outcomes, to explain these discrepant results.

Methods: In a retrospective cohort study conducted in 347 patients hospitalized for COVID-19 (Bichat Hospital, Paris, France, 23 January-29 April 2020), RAAS blocker exposure, as well as timing and reason for treatment modifications, were collected. The association between exposure and mortality within 30 days of hospital admission was analysed using logistic regression analysis adjusted for age, sex, and comorbidities.

Results: Median age was 61 [interquartile range, 51-72] years, 209 (60%) were male, 169 (49%) had a history of treated hypertension, and 117 (34%) received a RAAS blocker prior to hospitalization. RAAS blockers were discontinued within the first 7 days of hospital admission in 33% of previously treated patients (mostly driven by severity of the disease), with a corresponding mortality rate of 33%. Mortality was 8% when treatment was maintained or introduced, and 12% in patients never exposed. Adjusted odds ratios for association between exposure and mortality were 0.62 (95% confidence interval 0.25-1.48) based on chronic exposure and 0.25 (0.09-0.65) based on in-hospital exposure.

Conclusion: A 'healthy user-sick stopper' bias influences RAAS blocker prescription after hospital admission for COVID-19, and explains the seemingly favourable outcome associated with in-hospital treatment.
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http://dx.doi.org/10.1097/HJH.0000000000002658DOI Listing
February 2021

SARS-COV2 infection in 30 HIV-infected patients followed-up in a French University Hospital.

Int J Infect Dis 2020 Dec 26;101:49-51. Epub 2020 Sep 26.

AP-HP, Infectious and Tropical Diseases Department, Bichat-Claude Bernard University Hospital, Paris, France; Inserm U1137 IAME, Faculté de Médecine site Bichat Université de Paris, Paris, France.

Introduction: An acute respiratory disease caused by a novel coronavirus (SARSCOV2) is spreading from China since January 2020. Surprisingly, few cases of Covid-19 have been reported in people living with HIV (PLWHIV).

Methods: Here we present a series of 30 PLWHIV diagnosed for SARS-COV2 infection. The principal outcome was to describe clinical characteristics of this population.

Results: Eighteen (60%) patients were men, 10/30 (33,3%) women and 2/30 (6,7%) transgender women. Median age was 53,7 years (range 30-80 years) and 23/30 patients (76,7%) were born in a foreign country (out of France). The most common comorbidities were cardiovascular disease (11/30, 36,7%), hypertension (11/30, 36,7%), diabetes (9/30,30%) obesity (7/30, 23%) and chronic renal disease (5/30, 16,7%). Twenty (66,7%) patients presented overweight. Five patients (16,7%) had a Charlson comorbidity (Quan et al., 2011) score ≥3. Twenty-seven (90%) patients were virologically suppressed.CD4 count was >500cell/mm 3 in 23/30 (76,6%) patients. An antiviral treatment for SARS-COV2 was administered, in addition to HIV treatment, in 5/30 patients (16,3%). Twenty-four patients (80%) recovered from covid-19, 3/30 (10%) required invasive mechanical ventilation, 2/30 (6,7%) patients died and 4/30 (13,3%) patients were still hospitalized.

Conclusions: Most of the patients were virologically suppressed with CD4>500 mm3. Risk factors were the same as those described in other SARS-COV2 series, suggesting that HIV infection is probably not an independent risk factor for covid-19.
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http://dx.doi.org/10.1016/j.ijid.2020.09.1436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518976PMC
December 2020

Pre-exposure HIV prophylaxis (PrEP) among transgender women: 3 years of follow-up in a university hospital in Paris.

Sex Transm Infect 2020 Sep 2. Epub 2020 Sep 2.

Infectious Diseases, Hôpital Bichat-Claude-Bernard, Paris, France.

Objectives: The principal outcome was to describe clinical characteristics of a transgender male-to-female (TGW) cohort followed for pre-exposure HIV prophylaxis (PrEP).

Introduction: Few efforts and preventive interventions have targeted transgender population, despite them being at great risk of HIV infection.

Methods: This was a retrospective transgender male-to-female (TGW) cohort followed for PrEP at Bichat Hospital Sexual Health Clinic between February 2016 and January 2019.The principal outcome was to describe clinical characteristics of this TGW population: modalities of PrEP uptake, treatment adherence and tolerance, sanitary system retention, hormonal therapy and STIs.Data about age, ethnicity, language, sex work and sanitary healthcare insurance coverage were also collected.

Results: Forty-nine TGW were included, with a median age of 33 years; 43/49 (87.7%) were from South America and 43/49 (87.7%) were sex workers. Forty-four 44/49 TGW (89.7%) had no regular healthcare insurance coverage. Nineteen out of 49 (38.7%) had a history of STI in the last 12 months. Hormone intake was reported in 16/49 (32.60%). PrEP with oral TDF/FTC was prescribed on a daily basis for 45/49 TG (91.8%). Two TGW discontinued PrEP for gastrointestinal intolerance. No case of renal toxicity or HIV seroconversion has been reported. Retention rate was high (71.4%), but average follow-up was 9 months.

Conclusions: Our data showed a very vulnerable population, with a high proportion of migrants, sex workers and with a low healthcare insurance coverage. Retention rate was high (71.4%). Further multi-component interventions are needed to improve global sex health approach, PreP follow-up and sanitary system retention among TGW population.
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http://dx.doi.org/10.1136/sextrans-2020-054618DOI Listing
September 2020

Human plague: An old scourge that needs new answers.

PLoS Negl Trop Dis 2020 08 27;14(8):e0008251. Epub 2020 Aug 27.

Epidemiology and Clinical Research Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar.

Yersinia pestis, the bacterial causative agent of plague, remains an important threat to human health. Plague is a rodent-borne disease that has historically shown an outstanding ability to colonize and persist across different species, habitats, and environments while provoking sporadic cases, outbreaks, and deadly global epidemics among humans. Between September and November 2017, an outbreak of urban pneumonic plague was declared in Madagascar, which refocused the attention of the scientific community on this ancient human scourge. Given recent trends and plague's resilience to control in the wild, its high fatality rate in humans without early treatment, and its capacity to disrupt social and healthcare systems, human plague should be considered as a neglected threat. A workshop was held in Paris in July 2018 to review current knowledge about plague and to identify the scientific research priorities to eradicate plague as a human threat. It was concluded that an urgent commitment is needed to develop and fund a strong research agenda aiming to fill the current knowledge gaps structured around 4 main axes: (i) an improved understanding of the ecological interactions among the reservoir, vector, pathogen, and environment; (ii) human and societal responses; (iii) improved diagnostic tools and case management; and (iv) vaccine development. These axes should be cross-cutting, translational, and focused on delivering context-specific strategies. Results of this research should feed a global control and prevention strategy within a "One Health" approach.
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http://dx.doi.org/10.1371/journal.pntd.0008251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451524PMC
August 2020

Characterization and Treatment of SARS-CoV-2 in Nasal and Bronchial Human Airway Epithelia.

Cell Rep Med 2020 Jul;1(4):100059

CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France.

In the current COVID-19 pandemic effective treatments represents a major challenge. However, the scarcity of biologically relevant pre-clinical models of SARS-CoV-2 infection imposes a significant barrier for scientific and medical progress, including the rapid transition of potentially effective treatments to the clinical setting. We use reconstituted human airway epithelia to isolate and then characterize the viral infection kinetics, tissue-level remodeling of the cellular ultrastructure, and transcriptional early immune signatures induced by SARS-CoV-2 in a physiologically relevant model. Our results emphasize distinctive transcriptional immune signatures between nasal and bronchial HAE, both in terms of kinetics and intensity, hence suggesting putative intrinsic differences in the early response to SARS-CoV-2 infection. Most important, we provide evidence in human-derived tissues on the antiviral efficacy of remdesivir monotherapy and explore the potential of the remdesivir-diltiazem combination as an option worthy of further investigation to respond to the still-unmet COVID-19 medical need.
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http://dx.doi.org/10.1016/j.xcrm.2020.100059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373044PMC
July 2020

Hand hygiene improvement or antibiotic restriction to control the household transmission of extended-spectrum β-lactamase-producing Escherichia coli: a mathematical modelling study.

Antimicrob Resist Infect Control 2020 08 21;9(1):139. Epub 2020 Aug 21.

INSERM, Infection, Antimicrobials, Modelisation, Evolution (IAME), UMR 1137, F-75018, Paris, France.

Background: The best strategy to control ESBL-producing Escherichia coli (ESBL-EC) spread in the community is lacking.

Methods: We developed an individual-based transmission model to evaluate the impact of hand hygiene (HH) improvement and reduction in antibiotic use on the within-household transmission of ESBL-EC. We used data from the literature and incorporated key elements of ESBL-EC transmission such as the frequency and nature of contacts among household members, antibiotic use in the community and hand hygiene behaviour. We introduced in a household a single ESBL-EC colonised person and simulated the transmission dynamics of ESBL-EC over a one-year time horizon.

Results: The probability of ESBL-EC transmission depended on the household composition and the profile of the initial carrier. In the two-person household, the probability of ESBL-EC transmission was 5.3% (95% CI 5.0-5.6) or 6.6% (6.3-6.9) when the index person was a woman or a man, respectively. In a four-person household, the probability of transmission varied from 61.4% (60.9-62.0) to 68.8% (68.3-69.3) and was the highest when the index patient was the baby. Improving HH by 50% reduced the probability of transmission by 33-62%. Antibiotic restriction by 50% reduced the transmission by 2-6%.

Conclusions: The transmission of ESBL-EC is frequent in households and especially those with a baby. Antibiotic reduction had little impact on ESBL-EC. Improvement of hygiene in the community could help prevent transmission of ESBL-EC.
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http://dx.doi.org/10.1186/s13756-020-00803-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441222PMC
August 2020

A comparison of four serological assays for detecting anti-SARS-CoV-2 antibodies in human serum samples from different populations.

Sci Transl Med 2020 09 17;12(559). Epub 2020 Aug 17.

Molecular Genetics of RNA Viruses, Department of Virology, Institut Pasteur, CNRS UMR 3569, Paris, France.

It is of paramount importance to evaluate the prevalence of both asymptomatic and symptomatic cases of SARS-CoV-2 infection and their differing antibody response profiles. Here, we performed a pilot study of four serological assays to assess the amounts of anti-SARS-CoV-2 antibodies in serum samples obtained from 491 healthy individuals before the SARS-CoV-2 pandemic, 51 individuals hospitalized with COVID-19, 209 suspected cases of COVID-19 with mild symptoms, and 200 healthy blood donors. We used two ELISA assays that recognized the full-length nucleoprotein (N) or trimeric spike (S) protein ectodomain of SARS-CoV-2. In addition, we developed the S-Flow assay that recognized the S protein expressed at the cell surface using flow cytometry, and the luciferase immunoprecipitation system (LIPS) assay that recognized diverse SARS-CoV-2 antigens including the S1 domain and the carboxyl-terminal domain of N by immunoprecipitation. We obtained similar results with the four serological assays. Differences in sensitivity were attributed to the technique and the antigen used. High anti-SARS-CoV-2 antibody titers were associated with neutralization activity, which was assessed using infectious SARS-CoV-2 or lentiviral-S pseudotype virus. In hospitalized patients with COVID-19, seroconversion and virus neutralization occurred between 5 and 14 days after symptom onset, confirming previous studies. Seropositivity was detected in 32% of mildly symptomatic individuals within 15 days of symptom onset and in 3% of healthy blood donors. The four antibody assays that we used enabled a broad evaluation of SARS-CoV-2 seroprevalence and antibody profiling in different subpopulations within one region.
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http://dx.doi.org/10.1126/scitranslmed.abc3103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665313PMC
September 2020

Strengthening the global effort on COVID-19 research.

Lancet 2020 08 16;396(10248):375. Epub 2020 Jul 16.

UK Collaborative on Development Research, London NW1 2BE, UK. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(20)31598-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365643PMC
August 2020