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

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 (P < 10-4). 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, P < 10-3). 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.

Multivariate joint model under competing risks to predict death of hospitalized patients for SARS-CoV-2 infection.

During the coronavirus disease 2019 (COVID-19) pandemic, several clinical prognostic scores have been proposed and evaluated in hospitalized patients, relying on variables available at admission. However, capturing data collected from the longitudinal follow-up of patients during hospitalization may improve prediction accuracy of a clinical outcome. To answer this question, 327 patients diagnosed with COVID-19 and hospitalized in an academic French hospital between January and July 2020 are included in the analysis. Up to 59 biomarkers were measured from the patient admission to the time to death or discharge from hospital. We consider a joint model with multiple linear or nonlinear mixed-effects models for biomarkers evolution, and a competing risks model involving subdistribution hazard functions for the risks of death and discharge. The links are modeled by shared random effects, and the selection of the biomarkers is mainly based on the significance of the link between the longitudinal and survival parts. Three biomarkers are retained: the blood neutrophil counts, the arterial pH, and the C-reactive protein. The predictive performances of the model are evaluated with the time-dependent area under the curve (AUC) for different landmark and horizon times, and compared with those obtained from a baseline model that considers only information available at admission. The joint modeling approach helps to improve predictions when sufficient information is available. For landmark 6 days and horizon of 30 days, we obtain AUC [95% CI] 0.73 [0.65, 0.81] and 0.81 [0.73, 0.89] for the baseline and joint model, respectively (p = 0.04). Statistical inference is validated through a simulation study.

Compassionate Use of Remdesivir for Patients with Severe Covid-19.

BACKGROUND: Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. METHODS: We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day. RESULTS: Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. CONCLUSIONS: In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.).

Computerized decision support system (CDSS) use for surveillance of antimicrobial resistance in urinary tract infections in primary care.

BACKGROUND: Hospital-based surveillance of antimicrobial resistance may be irrelevant as a guide to antimicrobial use for urinary tract infections (UTIs) in primary care. OBJECTIVES: To highlight the value of online computerized decision support systems (CDSS) in providing information on the surveillance of antimicrobial resistance in community-acquired UTIs. METHODS: We collected the susceptibility profile for key antibiotics by type of UTI involving Escherichia coli from 2017 to 2020, using queries for UTI (Q-UTI) submitted to a French CDSS. We compared these results with those from the MedQual French surveillance system for community-acquired UTI and the European Antimicrobial Resistance Surveillance Network (EARS-NET) for invasive infections. RESULTS: We collected 43 591 Q-UTI, of which 10 192 (23%) involved E. coli: 40% cystitis, 32% male-UTI, and 27% pyelonephritis. Resistance was 41.3% (95% CI, 40.3%-42.2%) for amoxicillin, 16.6% (95% CI, 15.9%-17.3%) for fluoroquinolones, 6.6% (95% CI, 6.1%-7.0%) for third-generation cephalosporins (3GC), and 5.7% (95% CI, 5.2%-6.1%) for aminoglycosides. Resistance to amoxicillin was lower than that reported in MedQual (42.7%, P value = 0.004), and in EARS-NET (55.2%, P value < 0.001). For fluoroquinolones, resistance was higher than in MedQual (12.0%, P value < 0.001) and EARS-NET (15.8%, P value = 0.041). In complicated pyelonephritis and male UTI, fluoroquinolone resistance peaked at ∼20%. For 3GC, all UTI had higher resistance than in MedQual (3.5%, P value < 0.001), but lower than in EARS-NET (9.5%, P value < 0.001). Aminoglycoside resistance was not reported by MedQual, and was lower than in EARS-NET (7.1%, P value < 0.001). CONCLUSIONS: CDSS can inform prescribers in real-time about the ecology and surveillance of E. coli resistance in community-acquired UTI. In complicated upper UTIs, they can underline the risk of empirical use of fluoroquinolones and suggest preferential use of 3GC.

Increased risk of severe COVID-19 in hospitalized patients with SARS-CoV-2 Alpha variant infection: a multicentre matched cohort study.

BACKGROUND: The impact of the variant of concern (VOC) Alpha on the severity of COVID-19 has been debated. We report our analysis in France. METHODS: We conducted an exposed/unexposed cohort study with retrospective data collection, comparing patients infected by VOC Alpha to contemporaneous patients infected by historical lineages. Participants were matched on age (± 2.5 years), sex and region of hospitalization. The primary endpoint was the proportion of hospitalized participants with severe COVID-19, defined as a WHO-scale > 5 or by the need of a non-rebreather mask, occurring up to day 29 after admission. We used a logistic regression model stratified on each matched pair and accounting for factors known to be associated with the severity of the disease. RESULTS: We included 650 pairs of patients hospitalized between Jan 1, 2021, and Feb 28, 2021, in 47 hospitals. Median age was 70 years and 61.3% of participants were male. The proportion of participants with comorbidities was high in both groups (85.0% vs 90%, p = 0.004). Infection by VOC Alpha was associated with a higher odds of severe COVID-19 (41.7% vs 38.5%-aOR = 1.33 95% CI [1.03-1.72]). CONCLUSION: Infection by the VOC Alpha was associated with a higher odds of severe COVID-19.

Perceptions, current practices, and interventions of community pharmacists regarding antimicrobial stewardship: A qualitative study.

BACKGROUND: Community health care accounts for the vast majority of antibiotic use in Europe. Given the threat of antimicrobial resistance (AMR), there is an urgent need to develop new antimicrobial stewardship (AMS) interventions in primary care that could involve different health care providers, including community pharmacists. OBJECTIVES: This study aimed to explore the perceptions, currents practices, and interventions of community pharmacists regarding AMS. METHODS: Semistructured qualitative interviews were conducted with community pharmacists in France. Participants were recruited through a professional organization of community pharmacists combined with a snowballing technique. Interviews were audio recorded, transcribed, and analyzed using thematic analysis. The Consolidated Framework for Implementation Research was used while developing the interview guide and carrying out thematic analysis. RESULTS: Sixteen community pharmacists participated. All the respondents had good awareness about antimicrobial resistance and believed that community pharmacists had an important role in tackling AMR. Some barriers to community pharmacists' participation in AMS were identified such as difficult interactions with prescribers, lack of time, and lack of access to patient medical records and diagnosis. Increased patient education, audits and feedback of antibiotic prescribing, increased point-of-care testing, and delayed prescribing were interventions suggested by the pharmacists to improve antibiotic use in primary care. Strategies cited by participants to facilitate the implementation of such interventions are increased pharmacist-general practitioner collaboration, specialized training, clinical decision support tools, and financial incentives. CONCLUSION: This study suggests that community pharmacists could play a greater role in infection management and AMS interventions. Further interprofessional collaboration is needed to optimize antibiotic prescribing and utilization in community health care.

Long-Term Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infectiousness Among Three Immunocompromised Patients: From Prolonged Viral Shedding to SARS-CoV-2 Superinfection.

BACKGROUND: Guidelines for stopping coronavirus disease 2019 patient isolation are mainly symptom-based, with isolation for 10 to 20 days depending on their condition. METHODS: In this study, we describe 3 deeply immunocompromised patients, each with different clinical evolutions. We observed (1) the patients' epidemiological, clinical, and serological data, (2) infectiousness using viral culture, and (3) viral mutations accumulated over time. RESULTS: Asymptomatic carriage, symptom resolution, or superinfection with a second severe acute respiratory syndrome coronavirus 2 strain were observed, all leading to prolonged infectious viral shedding for several months. CONCLUSIONS: Understanding underlying mechanisms and frequency of prolonged infectiousness is crucial to adapt current guidelines and strengthen the use of systematic polymerase chain reaction testing before stopping isolation in immunocompromised populations.

Added value of rapid respiratory syndromic testing at point of care versus central laboratory testing: a controlled clinical trial.

BACKGROUND: Virus-associated respiratory infections are in the spotlight with the emergence of SARS-CoV-2 and the expanding use of multiplex PCR (mPCR). The impact of molecular testing as a point-of-care test (POCT) in the emergency department (ED) is still unclear. OBJECTIVES: To compare the impact of a syndromic test performed in the ED as a POCT and in the central laboratory on length of stay (LOS), antibiotic use and single-room assignment. METHODS: From 19 November 2019 to 9 March 2020, adults with acute respiratory illness seeking care in the ED of a large hospital were enrolled, with mPCR performed with a weekly alternation in the ED as a POCT (week A) or in the central laboratory (week B). RESULTS: 474 patients were analysed: 275 during A weeks and 199 during B weeks. Patient characteristics were similar. The hospital LOS (median 7 days during week A versus 7 days during week B, P = 0.29), the proportion of patients with ED-LOS <1 day (63% versus 60%, P = 0.57) and ED antibiotic prescription (59% versus 58%, P = 0.92) were not significantly different. Patients in the POCT arm were more frequently assigned a single room when having a positive PCR for influenza, respiratory syncytial virus and metapneumovirus [52/70 (74%) versus 19/38 (50%) in the central testing arm, P = 0.012]. CONCLUSIONS: Syndromic testing performed in the ED compared with the central laboratory failed to reduce the LOS or antibiotic consumption in patients with acute respiratory illness, but was associated with an increased single-room assignment among patients in whom a significant respiratory pathogen was detected.

Sociodemographic characteristics and transmission risk factors in patients hospitalized for COVID-19 before and during the lockdown in France.

BACKGROUND: The efficacy of lockdown in containing the COVID-19 pandemic has been reported in different studies. However, the impact on sociodemographic characteristics of individuals infected with SARS-CoV-2 has not been evaluated. The aim of this study was to describe the changes in sociodemographic characteristics of patients hospitalized for COVID-19 and to compare the transmission risk factors of COVID-19 before and during lockdown in France. METHODS: An observational retrospective study was conducted in a University Hospital in Paris, France. Data from patients hospitalized for COVID-19 in the Infectious Diseases Department between February 26 and May 11, 2020 were collected. The study population was divided into 2 groups: group A of patients infected before lockdown, and group B of patients infected during lockdown, considering a maximum incubation period of 14 days. Sociodemographic characteristics and transmission risk factors were compared between the 2 groups using Student's t-test for continuous variables and Chi-2 test or Fisher exact test for categorical variables. RESULTS: Three hundred eighty-three patients were included in the study, 305 (79.6%) in group A and 78 (20.4%) in group B. Patients in group A were significantly younger (60.0 versus (vs) 66.5 years (p = 0.03)). The professionally active population was larger in group A (44.3% vs 24.4%). There were significantly more non-French-speaking people in group B (16.7% vs 6.6%, p <  0.01). Most patients from group A had individual accommodation (92.8% vs 74.4%, p <  0.01). Contact with a relative was the main transmission risk factor in both groups (24.6% vs 33.3%, p = 0.16). Recent travel and large gathering were found only in group A. The proportion of people living in disadvantaged conditions, such as homeless people or people living in social housing, was significantly higher in group B (11.5% vs 4.3%, p = 0.03) as was the proportion of institutionalized individuals (14.1% vs 3.0%, p <  0.01). CONCLUSIONS: In this study conducted in patients hospitalized for COVID-19 in Paris, France, the likelihood of being infected despite the lockdown was higher for people who do not speak French, live in social housing, are homeless or institutionalized. Targeted measures have to be implemented to protect these populations.

Analysis of COVID-19 Transmission Sources in France by Self-Assessment Before and After the Partial Lockdown: Observational Study.

BACKGROUND: We developed a questionnaire on a web application for analyzing COVID-19 contamination circumstances in France during the second wave of the pandemic. OBJECTIVE: This study aims to analyze the impact on contamination characteristics before and after the second partial lockdown in France to adapt public health restrictions to further prevent pandemic surges. METHODS: Between December 15 and 24, 2020, after a national media campaign, users of the sourcecovid.fr web application were asked questions about their own or a close relative's COVID-19 contamination after August 15, 2020, in France. The data of the contamination's circumstances were assessed and compared before and after the second partial lockdown, which occurred on October 25, 2020, during the second wave of the pandemic and was ongoing on December 24, 2020. RESULTS: As of December 24, 2020, 441,000 connections on the web application were observed. A total of 2218 questionnaires were assessable for analysis. About 61.8% (n=1309) of the participants were sure of their contamination origin, and 38.2% (n=809) thought they knew it. The median age of users was 43.0 (IQR 32-56) years, and 50.7% (n=1073) were male. The median incubation time of the assessed cohort was 4.0 (IQR 3-5) days. Private areas (family's or friend's house) were the main source of contamination (1048/2090, 50.2%), followed by work colleagues (579/2090, 27.7%). The main time of day for the contamination was the evening (339/961, 35.3%) before the lockdown and was reduced to 18.2% (86/473) after the lockdown (P<.001). The person who transmitted the virus to the user before and after the lockdown was significantly different (P<.001): a friend (382/1317, 29% vs 109/773, 14.1%), a close relative (304/1317, 23.1% vs 253/773, 32.7%), or a work colleague (315/1317, 23.9% vs 264/773, 34.2%). The main location where the virus was transmitted to the users before and after the lockdown was significantly different too (P<.001): home (278/1305, 21.3% vs 194/760, 25.5%), work (293/1305, 22.5% vs 225/760, 29.6%), collective places (430/1305, 33% vs 114/760, 15%), and care centers (58/1305, 4.4% vs 74/760, 9.7%). CONCLUSIONS: Modalities of transmissions significantly changed before and after the second lockdown in France. The main sources of contamination remained the private areas and with work colleagues. Work became the main location of contamination after the lockdown, whereas contaminations in collective places were strongly reduced. TRIAL REGISTRATION: ClinicalTrials.gov NCT04670003; https://clinicaltrials.gov/ct2/show/NCT04670003.

A Self-Assessment Web-Based App to Assess Trends of the COVID-19 Pandemic in France: Observational Study.

BACKGROUND: We developed a self-assessment and participatory web-based triage app to assess the trends of the COVID-19 pandemic in France in March 2020. OBJECTIVE: We compared daily large-scale RT-PCR test results to monitor recent reports of anosmia through a web-based app to assess the dynamics of emergency department visits, hospitalizations, and intensive care unit (ICU) admissions among individuals with COVID-19 in France. METHODS: Between March 21 and November 18, 2020, users of the maladiecoronavirus.fr self-triage app were asked questions about COVID-19 symptoms. Data on daily hospitalizations, large-scale positive results on RT-PCR tests, emergency department visits, and ICU admission of individuals with COVID-19 were compared to data on daily reports of anosmia on the app. RESULTS: As of November 18, 2020, recent anosmia was reported 575,214 times from among approximately 13,000,000 responses. Daily anosmia reports during peak engagement with the app on September 16, 2020, were spatially correlated with the peak in daily COVID-19-related hospitalizations in November 2020 (Spearman rank correlation coefficient [ρ]=0.77; P<.001). This peak in daily anosmia reports was observed primarily among young adults (age range 18-40 years), being observed 49 days before the peak of hospitalizations that corresponded to the first wave of infections among the young population, followed by a peak in hospitalizations among older individuals (aged ≥50 years) in November 2020. The reduction in the daily reports of anosmia associated with the peaks in the number of cases preceded the reduction in daily hospitalizations by 10 and 9 days during the first and the second waves of infection, respectively, although the reduction in the positivity rates on RT-PCR tests preceded the reduction in daily hospitalizations by only 2 days during the second wave of infections. CONCLUSIONS: Data on daily reports of anosmia collected through a nationwide, web-based self-assessment app can be a relevant tool to anticipate surges in outbreaks, hospitalizations, and ICU admission during the COVID-19 pandemic. TRIAL REGISTRATION: ClinicalTrials.gov NCT04331171; https://clinicaltrials.gov/ct2/show/NCT04331171.

Evaluation of the QIAstat-Dx Respiratory SARS-CoV-2 Panel, the First Rapid Multiplex PCR Commercial Assay for SARS-CoV-2 Detection.

In the race to contain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), efficient detection and triage of infected patients must rely on rapid and reliable testing. In this work, we performed the first evaluation of the QIAstat-Dx respiratory SARS-CoV-2 panel (QIAstat-SARS) for SARS-CoV-2 detection. This assay is the first rapid multiplex PCR (mPCR) assay, including SARS-CoV-2 detection, and is fully compatible with a non-PCR-trained laboratory or point-of-care (PoC) testing. This evaluation was performed using 69 primary clinical samples (66 nasopharyngeal swabs [NPS], 1 bronchoalveolar lavage fluid sample [BAL], 1 tracheal aspirate sample, and 1 bronchial aspirate sample) comparing SARS-CoV-2 detection with the currently WHO-recommended reverse transcription-PCR (RT-PCR) (WHO-RT-PCR) workflow. Additionally, a comparative limit of detection (LoD) assessment was performed for QIAstat-SARS and WHO-RT-PCR using a quantified clinical sample. Compatibility of sample pretreatment for viral neutralization or viscous samples with the QIAstat-SARS system were also tested. The QIAstat-Dx respiratory SARS-CoV-2 panel demonstrated a sensitivity comparable to that of the WHO-recommended assay with a limit of detection at 1,000 copies/ml. The overall percent agreement between QIAstat-Dx SARS and WHO-RT-PCR on 69 clinical samples was 97% with a sensitivity of 100% (40/40) and specificity at 93% (27/29). No cross-reaction was encountered for any other respiratory viruses or bacteria included in the panel. The QIAstat-SARS rapid multiplex PCR panel provides a highly sensitive, robust, and accurate assay for rapid detection of SARS-CoV-2. This assay allows rapid decisions even in non-PCR-trained laboratory or point-of-care testing, allowing innovative organization.

A computerized decision support system (CDSS) for antibiotic prescription in primary care-Antibioclic: implementation, adoption and sustainable use in the era of extended antimicrobial resistance.

OBJECTIVES: To describe the implementation and use of a computerized decision support system (CDSS) for antibiotic prescription in primary care in France (Antibioclic). The CDSS targets 37 infectious diseases and has been freely available on a website since 2011. METHODS: Description and implementation of the architecture of a CDSS for antibiotic prescription in general practice. Analysis of the queries made between 2012 and 2018 on the CDSS by GPs. Analysis of two cross-sectional studies of users in 2014 and 2019. RESULTS: The number of queries increased from a median of 796/day [IQR, 578-989] in 2012 to 11 125/day [5592-12 505] in 2018. Unique users increased from 414/day [245-494] in 2012 to 5365/day [2891-5769] in 2018. Time taken to make a query was 2 min [1.9-2.1]. Among 3 542 347 queries in 2018, 78% were for adults. Six situations accounted for ≥50% of queries: cystitis; acute otitis media; acute sinusitis; community-acquired pneumonia; sore throat; and pyelonephritis. Queries concerned pathologies for which antibiotic prescription was necessary (64%), was conditional on additional clinical steps (34%) or was not recommended (2%). Most users (81%) were GPs, with median age of 38 years [31-52] and 58% were female. Among the 4016 GPs who responded to the surveys, the vast majority (96%) reported using the CDSS during the consultation, with 24% systematically using Antibioclic to initiate an antibiotic course and 93% having followed the CDSS recommendation for the latest prescription. Most GPs were comfortable using the CDSS in front of a patient. CONCLUSIONS: Antibioclic has been adopted and is widely used in primary care in France. Its interoperability could allow its adaptation and implementation in other countries.

Prevalence of tubulopathy and association with renal function loss in HIV-infected patients.

BACKGROUND: The incidence of chronic kidney disease (CKD) is 10 times higher in human immunodeficiency virus (HIV)-infected patients than in the general population. We explored the prevalence and determinants of proximal tubular dysfunction (PTD) in HIV-infected individuals, and assessed the impact of the tubulopathy on the estimated glomerular filtration rate (eGFR) outcome. METHODS: A cohort study was performed on 694 outpatients followed in a French centre to analyse the prevalence of PTD, the diagnosis performance of screening tools and the associated factors. eGFR was prospectively evaluated to analyse the predictive value of the tubulopathy on eGFR decrease. RESULTS: At inclusion, 14% of the patients presented with PTD and 5% with CKD. No individual tubular marker, including non-glomerular proteinuria, glycosuria dipstick or hypophosphataemia, registered sufficient performance to identify PTD. We found a significant interaction between tenofovir disoproxil fumarate exposure and ethnicity (P = 0.03) for tubulopathy risk. Tenofovir disoproxil fumarate exposure was associated with PTD in non-Africans [adjusted odds ratio (aOR) = 4.71, P < 10-3], but not in patients of sub-Saharan African origin (aOR = 1.17, P = 0.73). Among the 601 patients followed during a median of 4.3 years, 13% experienced an accelerated eGFR decline. Unlike microalbuminuria and glomerular proteinuria, tubulopathy was not associated with accelerated eGFR decline. CONCLUSION: PTD is not rare in HIV-infected individuals but is less frequent in sub-Saharan African patients and is associated with tenofovir disoproxil fumarate exposure only in non-Africans. Its diagnosis requires multiple biochemical testing and it is not associated with an accelerated eGFR decline.

Late viral or bacterial respiratory infections in lung transplanted patients: impact on respiratory function.

BACKGROUND: Respiratory infections are a major threat for lung recipients. We aimed to compare with a monocentric study the impact of late viral and bacterial respiratory infections on the graft function. METHODS: Patients, who survived 6 months or more following lung transplantation that took place between 2009 and 2014, were classified into three groups: a viral infection group (VIG) (without any respiratory bacteria), a bacterial infection group (BIG) (with or without any respiratory viruses), and a control group (CG) (no documented infection). Chronic lung allograft dysfunction (CLAD) and acute rejection were analysed 6 months after the inclusion in the study. RESULTS: Among 99 included lung recipients, 57 (58%) had at least one positive virological respiratory sample during the study period. Patients were classified as follows: 38 in the VIG, 25 in the BIG (among which 19 co-infections with a virus) and 36 in the CG. The BIG presented a higher initial deterioration in lung function (p = 0.05) than the VIG. But 6 months after the infection, only the VIG presented a median decrease of forced expiratory volume in 1 s; - 35 mL (IQR; - 340; + 80) in the VIG, + 140 mL (+ 60;+ 330) in the BIG and + 10 (- 84;+ 160) in the CG, p < 0.01. Acute rejection was more frequent in the VIG (n = 12 (32%)), than the BIG (n = 6 (24%)) and CG (n = 3 (8%)), p < 0.05, despite presenting no more CLAD (p = 0.21). CONCLUSIONS: Despite a less severe initial presentation, single viral respiratory infections seem to lead to a greater deterioration in lung function, and to more acute rejection, than bacterial infections.

Implementation of a Self-Triage Web Application for Suspected COVID-19 and Its Impact on Emergency Call Centers: Observational Study.

BACKGROUND: We developed a self-triage web application for COVID-19 symptoms, which was launched in France in March 2020, when French health authorities recommended all patients with suspected COVID-19 call an emergency phone number. OBJECTIVE: Our objective was to determine if a self-triage tool could reduce the burden on emergency call centers and help predict increasing burden on hospitals. METHODS: Users were asked questions about their underlying conditions, sociodemographic status, postal code, and main COVID-19 symptoms. Participants were advised to call an emergency call center if they reported dyspnea or complete loss of appetite for over 24 hours. Data on COVID-19-related calls were collected from 6 emergency call centers and data on COVID-19 hospitalizations were collected from Santé Publique France and the French Ministry of Health. We examined the change in the number of emergency calls before and after the launch of the web application. RESULTS: From March 17 to April 2, 2020, 735,419 questionnaires were registered in the study area. Of these, 121,370 (16.5%) led to a recommendation to call an emergency center. The peak number of overall questionnaires and of questionnaires leading to a recommendation to call an emergency center were observed on March 22, 2020. In the 17 days preceding the launch of the web application, emergency call centers in the study area registered 66,925 COVID-19-related calls and local hospitals admitted 639 patients for COVID-19; the ratio of emergency calls to hospitalizations for COVID-19 was 104.7 to 1. In the 17 days following the launch of the web application, there were 82,347 emergency calls and 6009 new hospitalizations for COVID-19, a ratio of 13.7 calls to 1 hospitalization (chi-square test: P<.001). CONCLUSIONS: The self-triage web application launch was followed by a nearly 10-fold increase in COVID-19-related hospitalizations with only a 23% increase in emergency calls. The peak of questionnaire completions preceded the peak of COVID-19-related hospitalizations by 5 days. Although the design of this study does not allow us to conclude that the self-triage tool alone contributed to the alleviation of calls to the emergency call centers, it does suggest that it played a role, and may be used for predicting increasing burden on hospitals. TRIAL REGISTRATION: ClinicalTrials.gov NCT04331171; https://clinicaltrials.gov/ct2/show/NCT04331171.

Epidemiological Observations on the Association Between Anosmia and COVID-19 Infection: Analysis of Data From a Self-Assessment Web Application.

BACKGROUND: We developed a self-assessment and participatory surveillance web application for coronavirus disease (COVID-19), which was launched in France in March 2020. OBJECTIVE: Our objective was to determine if self-reported symptoms could help monitor the dynamics of the COVID-19 outbreak in France. METHODS: Users were asked questions about underlying conditions, sociodemographic status, zip code, and COVID-19 symptoms. Depending on the symptoms reported and the presence of coexisting disorders, users were told to either stay at home, contact a general practitioner (GP), or call an emergency phone number. Data regarding COVID-19-related hospitalizations were retrieved from the Ministry of Health. RESULTS: As of March 29, 2020, the application was opened 4,126,789 times; 3,799,535 electronic questionnaires were filled out; and 2,477,174 users had at least one symptom. In total, 34.8% (n=1,322,361) reported no symptoms. The remaining users were directed to self-monitoring (n=858,878, 22.6%), GP visit or teleconsultation (n=1,033,922, 27.2%), or an emergency phone call (n=584,374, 15.4%). Emergency warning signs were reported by 39.1% of participants with anosmia, a loss of the sense of smell (n=127,586) versus 22.7% of participants without anosmia (n=1,597,289). Anosmia and fever and/or cough were correlated with hospitalizations for COVID-19 (Spearman correlation coefficients=0.87 and 0.82, respectively; P<.001 for both). CONCLUSIONS: This study suggests that anosmia may be strongly associated with COVID-19 and its severity. Despite a lack of medical assessment and virological confirmation, self-checking application data could be a relevant tool to monitor outbreak trends. TRIAL REGISTRATION: ClinicalTrials.gov NCT04331171; https://clinicaltrials.gov/ct2/show/NCT04331171.

Paving the Way for the Implementation of a Decision Support System for Antibiotic Prescribing in Primary Care in West Africa: Preimplementation and Co-Design Workshop With Physicians.

BACKGROUND: Suboptimal use of antibiotics is a driver of antimicrobial resistance (AMR). Clinical decision support systems (CDSS) can assist prescribers with rapid access to up-to-date information. In low- and middle-income countries (LMIC), the introduction of CDSS for antibiotic prescribing could have a measurable impact. However, interventions to implement them are challenging because of cultural and structural constraints, and their adoption and sustainability in routine clinical care are often limited. Preimplementation research is needed to ensure relevant adaptation and fit within the context of primary care in West Africa. OBJECTIVE: This study examined the requirements for a CDSS adapted to the context of primary care in West Africa, to analyze the barriers and facilitators of its implementation and adaptation, and to ensure co-designed solutions for its adaptation and sustainable use. METHODS: We organized a workshop in Burkina Faso in June 2019 with 47 health care professionals representing 9 West African countries and 6 medical specialties. The workshop began with a presentation of Antibioclic, a publicly funded CDSS for antibiotic prescribing in primary care that provides personalized antibiotic recommendations for 37 infectious diseases. Antibioclic is freely available on the web and as a smartphone app (iOS, Android). The presentation was followed by a roundtable discussion and completion of a questionnaire with open-ended questions by participants. Qualitative data were analyzed using thematic analysis. RESULTS: Most of the participants had access to a smartphone during their clinical consultations (35/47, 74%), but only 49% (23/47) had access to a computer and none used CDSS for antibiotic prescribing. The participants considered that CDSS could have a number of benefits including updating the knowledge of practitioners on antibiotic prescribing, improving clinical care and reducing AMR, encouraging the establishment of national guidelines, and developing surveillance capabilities in primary care. The most frequently mentioned contextual barrier to implementing a CDSS was the potential risk of increasing self-medication in West Africa, where antibiotics can be bought without a prescription. The need for the CDSS to be tailored to the local epidemiology of infectious diseases and AMR was highlighted along with the availability of diagnostic tests and antibiotics using national guidelines where available. Participants endorsed co-design involving all stakeholders, including nurses, midwives, and pharmacists, as central to any introduction of CDSS. A phased approach was suggested by initiating and evaluating CDSS at a pilot site, followed by dissemination using professional networks and social media. The lack of widespread internet access and computers could be circumvented by a mobile app with an offline mode. CONCLUSIONS: Our study provides valuable information for the development and implementation of a CDSS for antibiotic prescribing among primary care prescribers in LMICs and may, in turn, contribute to improving antibiotic use, clinical outcomes and decreasing AMR.

First cases of coronavirus disease 2019 (COVID-19) in France: surveillance, investigations and control measures, January 2020.

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.