Crise de la Covid-19 : les professionnels des établissements de santé en souffrance

Alors que l'infection au Sars-CoV-2 s'est rapidement propagée au niveau mondial, on a assisté à une mobilisation massive des établissements de santé pour accueillir l'afflux important de patients. La majorité des recherches ayant étudié l'impact psychologique de la crise sanitaire dans les établissements de santé se sont centrées sur les professionnels de première ligne. Mais, dans les faits, c'est l'ensemble des professionnels qui ont été affectés. Dans cet article, nous proposons d'effectuer une mise au point sur le vécu de ces professionnels dans les établissements de santé durant les premiers mois de la crise de la Covid-19. L'objectif de notre étude était d'identifier les facteurs de stress spécifiques, mais aussi communs à chacune des professions, en nous basant sur le discours de ces professionnels.Alternate :Since 2019, Covid-19 has rapidly spread worldwide, generating a pandemic. Healthcare organizations have been massively engaged in dealing with the large influx of patients. Most studies that considered the psychological impact of this crisis in health establishments focused on front-line professionals. However, recent literature showed that all professionals in healthcare organizations have been affected by the different stressors associated with this situation. Our research provides an update on the affective experience of these workers in French healthcare organizations during the first months of the COVID-19 crisis. Specifically, from a qualitative approach, we identified the common and specific stressors among the main stakeholders of such organizations.

A qualitative study of the perceptions and experiences of healthcare providers caring for critically ill patients during the first wave of the COVID-19 pandemic: A PsyCOVID-ICU substudy.

BACKGROUND: Intensive care unit (ICU) staff have faced unprecedented levels of stress, in the context of profound upheaval of their working environment due to the COVID-19 pandemic. We explored the perceptions of frontline ICU staff about the first wave of the COVID-19 pandemic, and how this experience impacted their personal and professional lives. METHODS: In a qualitative study as part of the PsyCOVID-ICU project, we conducted semi-structured interviews with a random sample of nurses and nurses' aides from 5 centres participating in the main PsyCOVID study. Interviews were recorded and fully transcribed, and analysed by thematic analysis. RESULTS: A total of 18 interviews were performed from 13 August to 6 October 2020; 13 were nurses, and 5 were nurses' aides. Thematic analysis revealed three major themes, namely: (1) Managing the home life; (2) Conditions in the workplace; and (3) the meaning of their profession. CONCLUSION: In this qualitative study investigating the experiences and perceptions of healthcare workers caring for critically ill patients during the first COVID-19 wave in France, the participants reported that the crisis had profound repercussions on both their personal and professional lives. The main factors affecting the participants were a fear of contamination, and the re-organisation of working conditions, against a background of a media "infodemic".

Mental Health Support for Hospital Staff during the COVID-19 Pandemic: Characteristics of the Services and Feedback from the Providers.

French authorities created mental health support services to accompany HCWs during the pandemic. We aimed to obtain feedback from staff providing these mental health support services within French hospitals to identify positive and negative features and avenues for improvement. A mixed-methods study was performed between 1 April and 30 June 2020. We contacted 77 centres to identify those providing mental health support services. We developed a questionnaire containing questions about the staff providing the service (quantitative part), with open questions to enable feedback from service providers (qualitative part). Of the 77 centres, 36 had mental health support services; 77.8% were created specifically for the epidemic. Services were staffed principally by psychologists, mainly used a telephone platform, and had a median opening time of 8 h/day. Thirty-seven professionals provided feedback, most aged 35-49 years. For 86.5%, it was their first time providing such support. Median self-reported comfort level was 8 (interquartiles 3-10), and 95% would do it again. Respondents reported (i) difficulties with work organisation, clinical situations, and lack of recognition and (ii) a desire for training. This study suggests that mental health support needs to be adapted to the needs of HCWs, both in terms of the content of the service and the timing of delivery.

A qualitative study of reinforcement workers' perceptions and experiences of working in intensive care during the COVID-19 pandemic: A PsyCOVID-ICU substudy.

PURPOSE: During the COVID pandemic, many hospitals had to mobilize reinforcement healthcare workers, especially in intensive care (ICUs). We investigated the perceptions and experiences of reinforcement workers deployed to ICUs, and the impact of deployment on their personal and professional lives. METHODS: For this qualitative study, a random sample of 30 reinforcement workers was drawn from 4 centres participating in the larger PsyCOVID-ICU study. Individual semi-structured interviews were held, recorded, transcribed and analyzed by thematic analysis. RESULTS: Thirty interviews were performed from April to May 2021 (22 nurses, 2 anesthesiology nurses, 6 nurses' aides). Average age was 36.8±9.5 years; 7 participants had no ICU experience. Four major themes emerged, namely: (1) Difficulties with integration, especially for those with no ICU experience; (2) lack of training; (3) difficulties with management, notably a feeling of insufficient communication; (4) Mental distress relating to the unusual work and fear of contaminating their entourage. CONCLUSION: Healthcare workers deployed as reinforcements to ICUs at the height of the pandemic had a unique experience of the crisis, and identified important gaps in organisation and preparation. They also suffered from a marked lack of training, given the stakes in the management of critically ill patients in the ICU.

Inhaled ciclesonide for outpatient treatment of COVID-19 in adults at risk of adverse outcomes: a randomised controlled trial (COVERAGE).

OBJECTIVES: To assess the efficacy of inhaled ciclesonide in reducing the risk of adverse outcomes in COVID-19 outpatients at risk of developing severe illness. METHODS: COVERAGE is an open-label, randomized controlled trial. Outpatients with documented COVID-19, risk factors for aggravation, symptoms for ≤7 days, and absence of criteria for hospitalization are randomly allocated to either a control arm or one of several experimental arms, including inhaled ciclesonide. The primary efficacy endpoint is COVID-19 worsening (hospitalization, oxygen therapy at home, or death) by Day 14. Other endpoints are adverse events, maximal follow-up score on the WHO Ordinal Scale for Clinical Improvement, sustained alleviation of symptoms, cure, and RT-PCR and blood parameter evolution at Day 7. The trial's Safety Monitoring Board reviewed the first interim analysis of the ciclesonide arm and recommended halting it for futility. The results of this analysis are reported here. RESULTS: The analysis involved 217 participants (control 107, ciclesonide 110), including 111 women and 106 men. Their median age was 63 years (interquartile range 59-68), and 157 of 217 (72.4%) had at least one comorbidity. The median time since first symptom was 4 days (interquartile range 3-5). During the 28-day follow-up, 2 participants died (control 2/107 [1.9%], ciclesonide 0), 4 received oxygen therapy at home and were not hospitalized (control 2/107 [1.9%], ciclesonide 2/110 [1.8%]), and 24 were hospitalized (control 10/107 [9.3%], ciclesonide 14/110 [12.7%]). In intent-to-treat analysis of observed data, 26 participants reached the composite primary endpoint by Day 14, including 12 of 106 (11.3%, 95% CI: 6.0%-18.9%) in the control arm and 14 of 106 (13.2%; 95% CI: 7.4-21.2%) in the ciclesonide arm. Secondary outcomes were similar for both arms. DISCUSSION: Our findings are consistent with the European Medicines Agency's COVID-19 task force statement that there is currently insufficient evidence that inhaled corticosteroids are beneficial for patients with COVID-19.

Risk and protective factors for the possible development of post-traumatic stress disorder among intensive care professionals in France during the first peak of the COVID-19 epidemic Factores de riesgo y factores protectores para el posible desarrollo de un trastorno de estrés postraumático en profesionales de cuidados intensivos en Francia durante la primera ola de la pandemia por la COVID-19 在 COVID-19 疫情第一个高峰期间, 法国重症监护专业人员可能发生创伤后应激障碍的风险和保护因素

Background Intensive care units (ICU) are among the healthcare services most affected by the COVID-19 crisis. Stressors related to insecurity, unpredictability, patient death and family distress are significant, and put healthcare workers (HCWs) at high risk of post-traumatic stress disorder (PTSD). The aims of this study were to measure the prevalence of post-traumatic stress disorder in HCWs and to identify risk factors and protective factors during the epidemic in France. Methods During the first peak of the epidemic (from 22 April to 13 May 2020), we assessed sources of stress (PS-ICU scale), mental health (GHQ-12) and coping strategies (Brief-COPE). Three months later (03 June to 6 July 2020), PTSD was assessed using the IES-R scale, with additional questions about sources of support. Data were collected using self-report questionnaires administered online. Results Among 2153 professionals who participated in the study, 20.6% suffered from potential PTSD, mostly intrusion symptoms. Risk factors for the development of PTSD were having experienced additional difficult events during the crisis, having a high level of psychological distress, a high level of perceived stress related to the workload and human resources issues, the emotional burden related to the patient and family, and stressors specific to COVID-19 during the first peak of the crisis. The use of positive thinking coping strategies decreased the relationship between perceived stress and the presence of PTSD, while social support seeking strategies increased the relationship. Finally, the HCWs preferred to use support from colleagues, relatives and/or a psychologist, and very few used the telephone hotlines. Conclusion The epidemic has had a strong traumatic impact on intensive care HCWs. Given the risk of PTSD, we need to consider implementing easily-accessible support services that focus on positive thinking coping strategies, during and after the crisis. HIGHLIGHTS The risk of PTSD is high among intensive care professionals. Perceived stress and psychological distress during the first peak of crisis increased the likelihood of subsequent PTSD. Support for professionals should be easily available and focused on positive thinking strategies.

Risk and protective factors for the possible development of post-traumatic stress disorder among intensive care professionals in France during the first peak of the COVID-19 epidemic.

Background: Intensive care units (ICU) are among the healthcare services most affected by the COVID-19 crisis. Stressors related to insecurity, unpredictability, patient death and family distress are significant, and put healthcare workers (HCWs) at high risk of post-traumatic stress disorder (PTSD). The aims of this study were to measure the prevalence of post-traumatic stress disorder in HCWs and to identify risk factors and protective factors during the epidemic in France. Methods: During the first peak of the epidemic (from 22 April to 13 May 2020), we assessed sources of stress (PS-ICU scale), mental health (GHQ-12) and coping strategies (Brief-COPE). Three months later (03 June to 6 July 2020), PTSD was assessed using the IES-R scale, with additional questions about sources of support. Data were collected using self-report questionnaires administered online. Results: Among 2153 professionals who participated in the study, 20.6% suffered from potential PTSD, mostly intrusion symptoms. Risk factors for the development of PTSD were having experienced additional difficult events during the crisis, having a high level of psychological distress, a high level of perceived stress related to the workload and human resources issues, the emotional burden related to the patient and family, and stressors specific to COVID-19 during the first peak of the crisis. The use of positive thinking coping strategies decreased the relationship between perceived stress and the presence of PTSD, while social support seeking strategies increased the relationship. Finally, the HCWs preferred to use support from colleagues, relatives and/or a psychologist, and very few used the telephone hotlines. Conclusion: The epidemic has had a strong traumatic impact on intensive care HCWs. Given the risk of PTSD, we need to consider implementing easily-accessible support services that focus on positive thinking coping strategies, during and after the crisis.

Antecedentes: Las unidades de cuidados intensivos (UCIs) se encuentran dentro de los servicios de salud más comprometidos por la crisis de la COVID-19. Los factores estresantes asociados a la inseguridad, la impredecibilidad, el fallecimiento de pacientes y la angustia familiar son considerables y colocan a los trabajadores de salud (TS) en un alto riesgo de trastorno de estrés postraumático (TEPT). Los objetivos de este estudio fueron el determinar la prevalencia del trastorno por estrés postraumático en TS e identificar los factores de riesgo y los factores protectores durante la epidemia en Francia.Métodos: Durante la primera ola de la epidemia (del 22 de abril al 13 de mayo del 2020) evaluamos fuentes de estrés (mediante la escala de percepción de factores estresantes en la UCI; PS-ICU en sus siglas en inglés), salud mental (mediante el cuestionario de salud general de 12 ítems; GHQ-12 en sus siglas en inglés) y estrategias de afrontamiento (mediante el inventario de la orientación del afrontamiento ante los problemas experimentados; Brief-COPE en sus siglas en inglés). Tres meses después (del 3 de junio al 6 de julio del 2020) se evaluó el TEPT mediante la escala de impacto del evento (IES-R en sus siglas en inglés) y con preguntas adicionales respecto a las fuentes de soporte. Se recolectó la información mediante cuestionarios de autoreporte realizados en línea.Resultados: De los 2.153 profesionales que participaron en el estudio, 20,6% padecían un potencial TEPT, predominando los síntomas intrusivos. Los factores de riesgo para el desarrollo del TEPT fueron el haber experimentado eventos difíciles adicionales durante la crisis, el tener un nivel elevado de angustia psicológica, un nivel alto de estrés percibido asociado a la carga laboral y a situaciones asociadas a los recursos humanos, la carga emocional relacionada al paciente y su familia, y los factores estresantes específicos de la COVID-19 durante la primera ola de la crisis. El uso del pensamiento positivo como estrategia de afrontamiento disminuía la relación entre el estrés percibido y la presencia del TEPT, mientras que las estrategias relacionadas con la búsqueda de soporte social incrementaban esta relación. Finalmente, los TS preferían emplear el soporte brindado por sus colegas, familiares y/o un psicólogo, mientras que muy pocos preferían el uso de líneas telefónicas de crisis.Conclusión: La epidemia ha tenido un fuerte impacto traumático sobre los TS de las UCIs. Dado el riesgo de TEPT, se necesita considerar la implementación de servicios de apoyo de fácil acceso que se enfoquen en el empleo del pensamiento positivo como estrategia de afrontamiento, tanto durante como después de la crisis.

Specific Features of the Coagulopathy Signature in Severe COVID-19 Pneumonia.

Rationale: COVID-19 displays distinct characteristics that suggest a unique pathogenesis. The objective of this study was to compare biomarkers of coagulopathy and outcomes in COVID-19 and non-COVID-19 patients with severe pneumonia. Methods: Thirty-six non-COVID-19 and 27 COVID-19 non-immunocompromised patients with severe pneumonia were prospectively enrolled, most requiring intensive care. Clinical and biological characteristics (including plasma biomarkers of coagulopathy) were compared. Results: At similar baseline severity, COVID-19 patients required mechanical ventilation (MV) for significantly longer than non-COVID-19 patients (p = 0.0049) and more frequently developed venous thrombotic complications (p = 0.031). COVID-19 patients had significantly higher plasma concentrations of soluble VCAM1 (sVCAM1) (5,739 ± 3,293 vs. 3,700 ± 2,124 ng/ml; p = 0.009), but lower levels of D-dimers, vWF-A2, sICAM1, sTREM1, VEGF, and P-selectin, compared to non-COVID-19 patients. Principal component analysis identified two main patterns, with a clear distinction between non-COVID-19 and COVID-19 patients. Multivariable regression analysis confirmed that sVCAM1 rising levels were independently associated with a longer duration of MV. Finally, we identified close correlations between sVCAM1 and some features of COVID-19 immune dysregulation (ie. CXCL10, GM-CSF, and IL-10). Conclusion: We identified specific features of the coagulopathy signature in severe COVID-19 patients, with higher plasma sVCAM1 levels, that were independently associated with the longer duration of mechanical ventilation. Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT03505281.

Are adipokines the missing link between obesity, immune response, and outcomes in severe COVID-19?

INTRODUCTION: Obesity is commonly reported in COVID-19 patients and is associated with poorer outcomes. It is suggested that leptin could be the missing link between obesity and severe COVID-19. Our study aimed to unravel the link between adipokines, COVID-19 status, immune response, and outcomes in severe pneumonia. METHODS: In this prospective observational single-center study, 63 immunocompetent patients with severe pneumonia (36 non-COVID-19 and 27 COVID-19) were enrolled, most required intensive care. Clinical and biological characteristics (glucose metabolism, plasma adipokines, and cytokine concentrations) and outcomes were compared. RESULTS: At similar baseline severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients (p = 0.0049). Plasma concentrations of leptin and adiponectin were respectively positively and negatively correlated with BMI and glucose metabolism (glycemia and insulinemia), but not significantly different between the two groups. Leptin levels were negatively correlated with IL-1ß and IL-6, but the adipokines were not correlated with most other inflammatory mediators, baseline severity (SOFA score), or the duration of mechanical ventilation. CONCLUSION: Adipokine levels were correlated with BMI but not with most inflammatory mediators, severity, or outcomes in severe pneumonia, regardless of the origin. The link between obesity, dysregulated immune response, and life-threatening COVID-19 requires further investigation. CLINICAL TRIAL: ClinicalTrials.gov: NCT03505281.

High plasma concentration of non-esterified polyunsaturated fatty acids is a specific feature of severe COVID-19 pneumonia.

COVID-19 pneumonia has specific features and outcomes that suggests a unique immunopathogenesis. Severe forms of COVID-19 appear to be more frequent in obese patients, but an association with metabolic disorders is not established. Here, we focused on lipoprotein metabolism in patients hospitalized for severe pneumonia, depending on COVID-19 status. Thirty-four non-COVID-19 and 27 COVID-19 patients with severe pneumonia were enrolled. Most of them required intensive care. Plasma lipid levels, lipoprotein metabolism, and clinical and biological (including plasma cytokines) features were assessed. Despite similar initial metabolic comorbidities and respiratory severity, COVID-19 patients displayed a lower acute phase response but higher plasmatic concentrations of non-esterified fatty acids (NEFAs). NEFA profiling was characterised by higher level of polyunsaturated NEFAs (mainly linoleic and arachidonic acids) in COVID-19 patients. Multivariable analysis showed that among severe pneumonia, COVID-19-associated pneumonia was associated with higher NEFAs, lower apolipoprotein E and lower high-density lipoprotein cholesterol concentrations, independently of body mass index, sequential organ failure (SOFA) score, and C-reactive protein levels. NEFAs and PUFAs concentrations were negatively correlated with the number of ventilator-free days. Among hospitalized patients with severe pneumonia, COVID-19 is independently associated with higher NEFAs (mainly linoleic and arachidonic acids) and lower apolipoprotein E and HDL concentrations. These features might act as mediators in COVID-19 pathogenesis and emerge as new therapeutic targets. Further investigations are required to define the role of NEFAs in the pathogenesis and the dysregulated immune response associated with COVID-19.Trial registration: NCT04435223.

The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome.

BACKGROUND: Although immune modulation is a promising therapeutic avenue in coronavirus disease 2019 (COVID-19), the most relevant targets remain to be found. COVID-19 has peculiar characteristics and outcomes, suggesting a unique immunopathogenesis. METHODS: Thirty-six immunocompetent non-COVID-19 and 27 COVID-19 patients with severe pneumonia were prospectively enrolled in a single center, most requiring intensive care. Clinical and biological characteristics (including T cell phenotype and function and plasma concentrations of 30 cytokines) and outcomes were compared. RESULTS: At similar baseline respiratory severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients (15 [7-22] vs. 4 (0-15) days; p = 0.0049). COVID-19 patients had lower levels of most classical inflammatory cytokines (G-CSF, CCL20, IL-1ß, IL-2, IL-6, IL-8, IL-15, TNF-α, TGF-ß), but higher plasma concentrations of CXCL10, GM-CSF and CCL5, compared to non-COVID-19 patients. COVID-19 patients displayed similar T-cell exhaustion to non-COVID-19 patients, but with a more unbalanced inflammatory/anti-inflammatory cytokine response (IL-6/IL-10 and TNF-α/IL-10 ratios). Principal component analysis identified two main patterns, with a clear distinction between non-COVID-19 and COVID-19 patients. Multivariate regression analysis confirmed that GM-CSF, CXCL10 and IL-10 levels were independently associated with the duration of mechanical ventilation. CONCLUSION: We identified a unique cytokine response, with higher plasma GM-CSF and CXCL10 in COVID-19 patients that were independently associated with the longer duration of mechanical ventilation. These cytokines could represent the dysregulated immune response in severe COVID-19, as well as promising therapeutic targets. ClinicalTrials.gov: NCT03505281.

CXCL10 could drive longer duration of mechanical ventilation during COVID-19 ARDS.

BACKGROUND: COVID-19-related ARDS has unique features when compared with ARDS from other origins, suggesting a distinctive inflammatory pathogenesis. Data regarding the host response within the lung are sparse. The objective is to compare alveolar and systemic inflammation response patterns, mitochondrial alarmin release, and outcomes according to ARDS etiology (i.e., COVID-19 vs. non-COVID-19). METHODS: Bronchoalveolar lavage fluid and plasma were obtained from 7 control, 7 non-COVID-19 ARDS, and 14 COVID-19 ARDS patients. Clinical data, plasma, and epithelial lining fluid (ELF) concentrations of 45 inflammatory mediators and cell-free mitochondrial DNA were measured and compared. RESULTS: COVID-19 ARDS patients required mechanical ventilation (MV) for significantly longer, even after adjustment for potential confounders. There was a trend toward higher concentrations of plasma CCL5, CXCL2, CXCL10, CD40 ligand, IL-10, and GM-CSF, and ELF concentrations of CXCL1, CXCL10, granzyme B, TRAIL, and EGF in the COVID-19 ARDS group compared with the non-COVID-19 ARDS group. Plasma and ELF CXCL10 concentrations were independently associated with the number of ventilator-free days, without correlation between ELF CXCL-10 and viral load. Mitochondrial DNA plasma and ELF concentrations were elevated in all ARDS patients, with no differences between the two groups. ELF concentrations of mitochondrial DNA were correlated with alveolar cell counts, as well as IL-8 and IL-1ß concentrations. CONCLUSION: CXCL10 could be one key mediator involved in the dysregulated immune response. It should be evaluated as a candidate biomarker that may predict the duration of MV in COVID-19 ARDS patients. Targeting the CXCL10-CXCR3 axis could also be considered as a new therapeutic approach. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03955887.

Home Treatment of Older People with Symptomatic SARS-CoV-2 Infection (COVID-19): A structured Summary of a Study Protocol for a Multi-Arm Multi-Stage (MAMS) Randomized Trial to Evaluate the Efficacy and Tolerability of Several Experimental Treatments to Reduce the Risk of Hospitalisation or Death in outpatients aged 65 years or older (COVERAGE trial).

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).