Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 25
Filter
1.
Clin Microbiol Infect ; 2022 Mar 15.
Article in English | MEDLINE | ID: covidwho-1739639

ABSTRACT

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, randomised controlled trial. Outpatients with documented COVID-19, risk factors for aggravation, symptoms <7 days and absence of criteria for hospitalisation 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 (hospitalisation, oxygen therapy at home, or death) by Day 14. Other endpoints are adverse events, maximal follow-up score on the WHO OSCI, 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 (IQR) 59-68]. 157/217 (72.4%) had at least one comorbidity. The median time since first symptom was 4 days [IQR 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 hospitalised (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 Day14, including 12/106 (11. 3%, 95% CI 6.0 to 18.9%) in the control arm and 14/106 (13.2%; 95% CI 7.4 to 21.2%) in the ciclesonide arm. Secondary outcomes were similar for both arms. CONCLUSIONS: Our findings are consistent with the European Medicines Agency's COVID-19 taskforce statement that there is currently insufficient evidence that inhaled corticosteroids are beneficial for people with COVID-19.

2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-319199

ABSTRACT

Background: The DYNAMIC study is based on three properties of tetracyclines. (1) Tetracyclines are known to chelate zinc from matrix metalloproteinases. It is possible their chelating activity may help inhibit COVID-19 infection by limiting its ability to replicate in the host. (2) As seen with dengue virus, tetracyclines may also be able to inhibit the replication of positive polarity single-stranded RNA viruses, such as COVID-19. (3) Tetracyclines are also modulators of innate immunity (anti-inflammatory activity), a property that has been used to treat inflammatory skin diseases for many years. They could therefore participate in limiting the cytokine storm induced by COVID-19. Moreover, the lipophilic nature of tetracyclines and their strong pulmonary penetration could allow them to inhibit viral replication at this level. Among the tetracyclines, doxycycline has three advantages: its long safety history (side effects are uncommon with no notable risks), its short treatment duration and its low cost. Methods: The trial will involve 330 patients who are positive for SARS-CoV-2 infection and have one or more risk factors for worsening the disease. These patients will be included as outpatients for early treatment of illness. For logistical reasons and in order to be able to standardise the study as much as possible, recruitment will take place in 6 hospital departments covering the whole of France. For 14 days they will be given either 200mg of doxycycline a day or placebo. Our hypothesis is a considerable reduction in the number of patients hospitalised due to COVID-19 thanks to the treatment of doxycycline. Discussion: This study could have an impact on the overcrowding of patients with COVID-19 at the hospital which is one of the major world-wide problems of this pandemic. This treatment would therefore contribute to supporting the deconfinement strategy by blocking the viral infection early and reducing the infectious period.Trial Registration: On ClinicalTrials.gov, registration number NCT04371952, first published on 30 April 2020.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-317933

ABSTRACT

Background: The pathogenesis of severe COVID-19 is frequently associated with an uncontrolled inflammatory response. 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.Methods: 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 features were assessed.Findings: Despite similar initial metabolic comorbidities and respiratory severity, COVID-19 patients displayed a lower acute phase response with 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, suggesting an increase in phospholipase A2 activity. 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.Trial Registration: NCT04435223Funding Statement: This study was supported by grant (MN) from the COVIDOLIP – AOIc2020 (Institutional grant), by the INSERM (Centre de Recherche UMR 1231) and the ANR Investissements d’Avenir Grant (ANR-11 LABX-0021-01, Labex Lipstic).Declaration of Interest: The authors declare no existing conflict of interest.Ethics Approval Statement: The study fulfilled legal and ethics requirements: Approval was obtained from the CPP (Comité de Protection des Personnes SUD MEDITERRANEE V;2017-A03404-49) for the original study and an amendment was obtained to include supplementary patients with severe COVID-19. All subjects (or their legal representatives) received written information and provided their consent to participate.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-304820

ABSTRACT

Background: The antiviral efficacy of remdesivir is still controversial. We aimed at evaluating its clinical effectiveness in patients with COVID-19 requiring oxygen and/or ventilator support.Methods: In this European multicentre, open-label, parallel-group, randomised, controlled trial in adults hospitalised with COVID-19 (DisCoVeRy, NCT04315948;EudraCT2020-000936-23), participants were randomly allocated to receive usual standard of care alone or in combination with intravenous remdesivir (200 mg on day 1, then 100 mg once-daily for 9 days or until discharge). Treatment assignation was performed via web-based randomisation stratified on illness severity and administrative European region. The primary outcome was the clinical status at day 15 measured by the WHO 7-point ordinal scale, assessed in the intention-to-treat population.Findings: Between March 22nd, 2020 and January 21st, 2021, 857 participants were randomised to one of the two arms in 5 European countries and 832 participants were included for the evaluation of remdesivir (control, n=418;remdesivir, n=414). There was no difference in the clinical status neither at day 15 between treatment groups (OR for remdesivir, 0.98, 95% CI, 0.77 to 1.25, P=0.85) nor at day 29. The proportion of deaths at day 28 was not significantly different between control (8.9%) and remdesivir (8.2%) treatment groups (OR for remdesivir, 0.93 95%CI 0.57 to 1.52, P=0.77). There was also no difference on SARS-CoV-2 viral kinetics (effect of remdesivir on viral load slope, -0.004 log10 cp/10,000 cells/day, 95% CI, -0.03 to 0.02, P=0.75). There was no significant difference in the occurrence of Serious Adverse Events between treatment groups.Interpretation: The use of remdesivir for the treatment of hospitalised patients with COVID-19 was not associated with clinical improvement at day 15 or day 29, nor with a reduction in mortality, nor with a reduction in SARS-CoV-2 RNA.Trial Registration: DisCoVeRy, NCT04315948;EudraCT2020-000936-23Funding: European Union Commission, French Ministry of Health, DIM One Health Île-de-France, REACTing, Fonds Erasme-COVID-ULB;Belgian Health Care Knowledge Centre (KCE)Declaration of Interests: Dr. Costagliola reports grants and personal fees from Janssen, personal fees from Gilead, outside the submitted work. Dr. Mentré reports grants from INSERM Reacting (French Government), grants from Ministry of Health (French Government), grants from European Commission, during the conduct of the study;grants from Sanofi, grants from Roche, outside the submitted work. Dr. Hites reports grants from The Belgian Center for Knowledge (KCE), grants from Fonds Erasme-COVID-ULB, during the conduct of the study;personal fees from Gilead, outside the submitted work. Dr. Mootien reports non-financial support from GILEAD, outside the submitted work. Dr. Gaborit reports non-financial support from Gilead, non- financial support from MSD, outside the submitted work. Dr. Botelho-Nevers reports other from Pfizer, other from Janssen, outside the submitted work. Dr. Lacombe reports personal fees and non-financial support from Gilead, personal fees and non-financial support from Janssen, personal fees and non-financial support from MSD, personal fees and non-financial support from ViiV Healthcare, personal fees and non-financial support from Abbvie, during the conduct of the study. Dr. Wallet reports personal fees and non-financial support from Jazz pharmaceuticals, personal fees and non-financial support from Novartis, personal fees and nonPage financial support from Kite-Gilead, outside the submitted work. Dr. Kimmoun reports personal fees from Aguettan, personal fees from Aspen, outside the submitted work. Dr. Thiery reports personal fees from AMGEN, outside the submitted work. Dr. Burdet reports personal fees from Da Volterra, personal fees from Mylan Pharmaceuticals, outside the submitted work. Dr. Poissy reports personal fees from Gilead for lectures, outside the submitted work. Dr. Goehringer reports personal fees from G lead Sciences, non-financial support from Gilead Sciences, grants from Biomerieux, non-financial support from Pfizer, outside the submitted work. Dr. Peytavin reports personal fees from Gilead Sciences, personal fees from Merck France, personal fees from ViiV Healthcare, personal fees from TheraTechnologies, outside the submitted work. Dr. Danion reports personal fees from Gilead, outside the submitted work. Dr. Raffi reports personal fees from Gilead, personal fees from Janssen, personal fees from MSD, personal fees from Abbvie, personal fees from ViiV Healthcare, personal fees from Theratechnologies, personal fees from Pfizer, outside the submitted work. Dr. Gallien reports personal fees from Gilead, personal fees from Pfizer, personal fees from ViiV, personal fees from MSD, outside the submitted work;and has received consulting fee from Gilead in August 2020 to check the registration file of remdesivir for the French administration. Dr. Nseir reports personal fees from MSD, personal fees from Pfizer, personal fees from Gilead, personal fees from Biomérieux, personal fees from BioRad, outside the submitted work. Dr. Lefèvre reports personal fees from Mylan, personal fees from Gilead, outside the submitted work. Dr. Guedj reports personal fees from Roche, outside the submitted work. Other authors have nothing to disclose.Ethics Approval Statement: The trial was approved by the Ethics Committee (CPP Ile-de-France-III, approval #20.03.06.51744), and is sponsored by the Institut national de la santé et de la recherche médicale (Inserm, France);it was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all included participants (or their legal representatives if unable to consent). The present analysis is based on the protocol v11.0 of December 12th, 2020.

5.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327725

ABSTRACT

Objectives: We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-beta-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in COVID-19 inpatients requiring oxygen and/or ventilatory support. While preliminary results were previously published, we present here the final results, following completion of the data monitoring. Methods We conducted a phase 3 multi-centre open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), add-on trial to Solidarity ( NCT04315948 , EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO 7-point ordinal scale. Secondary outcomes included SARS-CoV-2 quantification in respiratory specimens, pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, which were stopped prematurely. Results The intention-to-treat population included 593 participants (lopinavir/ritonavir, n=147;lopinavir/ritonavir-IFN-beta-1a, n=147;hydroxychloroquine, n=150;control, n=149), among whom 421 (71.0%) were male, the median age was 64 years (IQR, 54-71) and 214 (36.1%) had a severe disease. The day 15 clinical status was not improved with investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.82, (95% confidence interval [CI] 0.54-1.25, P=0.36);lopinavir/ritonavir-IFN-beta-1a versus control, aOR 0.69 (95%CI 0.45-1.05, P=0.08);hydroxychloroquine versus control, aOR 0.94 (95%CI 0.62-1.41, P=0.76). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of Serious Adverse Events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms. Conclusion In adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir-IFN-beta-1a and hydroxychloroquine did not improve the clinical status at day 15, nor SARS-CoV-2 clearance in respiratory tract specimens.

6.
Cancers (Basel) ; 13(24)2021 Dec 14.
Article in English | MEDLINE | ID: covidwho-1572372

ABSTRACT

Few studies have investigated the link between SARS-CoV-2 and health restrictions and its effects on the health of lung cancer (LC) patients. The aim of this study was to assess the impact of the SARS-CoV-2 epidemic on surgical activity volume, postoperative complications and in-hospital mortality (IHM) for LC resections in France. All data for adult patients who underwent pulmonary resection for LC in France in 2020, collected from the national administrative database, were compared to 2018-2019. The effect of SARS-CoV-2 on the risk of IHM and severe complications within 30 days among LC surgery patients was examined using a logistic regression analysis adjusted for age, sex, comorbidities and type of resection. There was a slight decrease in the volume of LC resections in 2020 (n = 11,634), as compared to 2018 (n = 12,153) and 2019 (n = 12,227), with a noticeable decrease in April 2020 (the peak of the first wave of epidemic in France). We found that SARS-CoV-2 (0.43% of 2020 resections) was associated with IHM and severe complications, with, respectively, a sevenfold (aOR = 7.17 (3.30-15.55)) and almost a fivefold (aOR = 4.76 (2.31-9.80)) increase in risk. Our study suggests that LC surgery is feasible even during a pandemic, provided that general guidance protocols edited by the surgical societies are respected.

7.
Respir Res ; 22(1): 298, 2021 Nov 20.
Article in English | MEDLINE | ID: covidwho-1526637

ABSTRACT

BACKGROUND: This study assessed the impact of the COVID-19 epidemic on overall hospitalizations for pulmonary embolism (PE) in France in comparison with previous years, and by COVID-19 and non-COVID-19 status. METHODS: Hospitalization data (2017-2020) were extracted from the French National Discharge database (all public and private hospitals). We included all patients older than 18 years hospitalized during the 3 years and extracted PE status and COVID-19 status (from March 2020). Age, sex and risk factors for PE (such as obesity, cancer) were identified. We also extracted transfer to an intensive care unit (ICU) and hospital death. The number of PE and the frequency of death in patients in 2019 and 2020 were described by month and by COVID-19 status. Logistic regressions were performed to identify the role of COVID-19 among other risk factors for PE in hospitalized patients. RESULTS: The overall number of patients hospitalized with PE increased by about 16% in 2020 compared with 2019, and mortality also increased to 10.3% (+ 1.2%). These increases were mostly linked to COVID-19 waves, which were associated with PE hospitalization in COVID-19 patients (PE frequency was 3.7%; 2.8% in non-ICU and 8.8% in ICU). The final PE odds ratio for COVID-19 hospitalized patients was 4 compared with other hospitalized patients in 2020. The analyses of PE in non-COVID-19 patients showed a 2.7% increase in 2020 compared with the previous three years. CONCLUSION: In 2020, the overall number of patients hospitalized with PE in France increased compared to the previous three years despite a considerable decrease in scheduled hospitalizations. Nevertheless, proactive public policy focused on the prevention of PE in all patients should be encouraged.


Subject(s)
COVID-19/epidemiology , COVID-19/prevention & control , Communicable Disease Control/trends , Hospitalization/trends , Pulmonary Embolism/epidemiology , Pulmonary Embolism/therapy , Aged , Aged, 80 and over , Cohort Studies , Communicable Disease Control/methods , Female , France/epidemiology , Humans , Male , Middle Aged , Pulmonary Embolism/diagnosis , Retrospective Studies
8.
Front Med (Lausanne) ; 8: 675191, 2021.
Article in English | MEDLINE | ID: covidwho-1369670

ABSTRACT

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.

9.
Int J Obes (Lond) ; 45(9): 2126-2131, 2021 09.
Article in English | MEDLINE | ID: covidwho-1249201

ABSTRACT

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.


Subject(s)
Adipokines/immunology , COVID-19/immunology , Obesity/complications , Adipokines/blood , Adiponectin , Aged , Cytokines , Female , Humans , Immunity , Leptin , Male , Middle Aged , Prospective Studies , Severity of Illness Index
10.
Clin Microbiol Infect ; 27(12): 1826-1837, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1242906

ABSTRACT

OBJECTIVES: We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-ß-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in coronavirus 2019 disease (COVID-19) inpatients requiring oxygen and/or ventilatory support. METHODS: We conducted a phase III multicentre, open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), an add-on to the Solidarity trial (NCT04315948, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO seven-point ordinal scale. Secondary outcomes included quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory specimens and pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, trials of which were stopped prematurely. RESULTS: The intention-to-treat population included 583 participants-lopinavir/ritonavir (n = 145), lopinavir/ritonavir-IFN-ß-1a (n = 145), hydroxychloroquine (n = 145), control (n = 148)-among whom 418 (71.7%) were male, the median age was 63 years (IQR 54-71), and 211 (36.2%) had a severe disease. The day-15 clinical status was not improved with the investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.83, (95% confidence interval (CI) 0.55-1.26, p 0.39), lopinavir/ritonavir-IFN-ß-1a versus control, aOR 0.69 (95%CI 0.45-1.04, p 0.08), and hydroxychloroquine versus control, aOR 0.93 (95%CI 0.62-1.41, p 0.75). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of serious adverse events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms. CONCLUSION: In adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir-IFN-ß-1a and hydroxychloroquine improved neither the clinical status at day 15 nor SARS-CoV-2 clearance in respiratory tract specimens.


Subject(s)
Antiviral Agents , COVID-19 , Hydroxychloroquine/therapeutic use , Interferon beta-1a/therapeutic use , Lopinavir/therapeutic use , Ritonavir/therapeutic use , Adult , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Drug Combinations , Female , Humans , Male , Middle Aged , Treatment Outcome
11.
Sci Rep ; 11(1): 10824, 2021 05 24.
Article in English | MEDLINE | ID: covidwho-1242049

ABSTRACT

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.


Subject(s)
COVID-19/pathology , Fatty Acids, Nonesterified/blood , Aged , Apolipoproteins E/blood , Arachidonic Acids/blood , COVID-19/blood , COVID-19/virology , Cholesterol, HDL/blood , Cytokines/blood , Female , Humans , Linoleic Acids/blood , Male , Middle Aged , Principal Component Analysis , SARS-CoV-2/isolation & purification , Severity of Illness Index
12.
Eur Respir J ; 58(6)2021 12.
Article in English | MEDLINE | ID: covidwho-1238699

ABSTRACT

BACKGROUND: Influenza epidemics were initially considered to be a suitable model for the COVID-19 epidemic, but there is a lack of data concerning patients with chronic respiratory diseases (CRDs), who were supposed to be at risk of severe forms of COVID-19. METHODS: This nationwide retrospective cohort study describes patients with prior lung disease hospitalised for COVID-19 (March-April 2020) or influenza (2018-2019 influenza outbreak). We compared the resulting pulmonary complications, need for intensive care and in-hospital mortality depending on respiratory history and virus. RESULTS: In the 89 530 COVID-19 cases, 16.03% had at least one CRD, which was significantly less frequently than in the 45 819 seasonal influenza patients. Patients suffering from chronic respiratory failure, chronic obstructive pulmonary disease, asthma, cystic fibrosis and pulmonary hypertension were under-represented, contrary to those with lung cancer, sleep apnoea, emphysema and interstitial lung diseases. COVID-19 patients with CRDs developed significantly more ventilator-associated pneumonia and pulmonary embolism than influenza patients. They needed intensive care significantly more often and had a higher mortality rate (except for asthma) when compared with patients with COVID-19 but without CRDs or patients with influenza. CONCLUSIONS: Patients with prior respiratory diseases were globally less likely to be hospitalised for COVID-19 than for influenza, but were at higher risk of developing severe COVID-19 and had a higher mortality rate compared with influenza patients and patients without a history of respiratory illness.


Subject(s)
COVID-19 , Influenza, Human , Hospital Mortality , Humans , Influenza, Human/complications , Influenza, Human/epidemiology , Retrospective Studies , SARS-CoV-2
13.
Clin Microbiol Infect ; 27(7): 1041.e1-1041.e4, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1225180

ABSTRACT

OBJECTIVES: Persistent COVID-19 symptoms have been reported up to 3 months after hospital discharge. Little is known on the frequency and the nature of persistent symptoms beyond 3 months. Here we have assessed, in the longitudinal prospective French COVID-19 cohort, symptoms that persisted 6 months after admission for COVID-19. METHODS: Hospitalized patients with virologically confirmed COVID-19 were enrolled. Follow-up was planned with a physician's visit at month (M)3 and M6 after admission. Associations between persistence of symptoms at M6 and clinical characteristics at admission were assessed through bivariate and multivariate logistic regression. RESULTS: M6 data were available for 1137 participants. Median age was 61 years (IQR 51-71) and 288 (29%, 95% CI 26-32%) were admitted to intensive care unit (ICU) during the acute phase. Six hundred and fifty-five (68%, 95% CI 65-71%) and 639 (60%, 95% CI 57-63%) participants had at least one symptom at M3 and M6 visit, respectively, mostly fatigue, dyspnoea, joint pain and myalgia. At M6, 255 (24%, 95% CI 21-27%) of participants had three or more persistent symptoms. The presence of three or more symptoms at M6 was independently associated with female gender (adjusted odds ratio (aOR) 2.40, 95% CI 1.75-3.30), having three or more symptoms at admission (aOR 2.04, 95% CI 1.45-2.89) and ICU admission/transfer during acute phase (aOR 1.55, 95% CI 1.09-2.18), but not significantly with age or having two or more comorbidities. One hundred and twenty-five (29%, 95% CI 25-34%) of those who initially had a professional occupation were not back to work at M6. DISCUSSION: A fourth of individuals admitted to hospital for COVID-19 still had three or more persistent symptoms at M6. Longitudinal follow-up of individuals with severe COVID-19 is warranted to better understand the pathophysiology underlying this long-term persistence.


Subject(s)
COVID-19/epidemiology , Symptom Assessment/statistics & numerical data , Aged , COVID-19/virology , Comorbidity , Female , Follow-Up Studies , France/epidemiology , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged , Pandemics , Patient Discharge , Prevalence , Prospective Studies , Risk Factors , SARS-CoV-2/isolation & purification
16.
Fundam Clin Pharmacol ; 35(6): 1141-1158, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1194121

ABSTRACT

AIMS: The role of renin-angiotensin-aldosterone system (RAAS) blockers on the course of coronavirus disease 2019 (COVID-19) is debated. We assessed the association between chronic use of RAAS blockers and mortality among inpatients with COVID-19 and explored reasons for discrepancies in the literature. METHODS AND RESULTS: We included adult hypertensive patients from a prospective nationwide cohort of 3512 inpatients with COVID-19 up to June 30, 2020. Cox proportional hazard models with various adjustment or propensity weighting methods were used to estimate the hazard ratios (HR) of 30-day mortality for chronic users versus non-users of RAAS blockers. We analyzed data of 1160 hypertensive patients: 719 (62%) were male and 777 (67%) were older than 65 years. The main comorbidities were diabetes (n = 416, 36%), chronic cardiac disease (n = 401, 35%), and obesity (n = 340, 29%); 705 (61%) received oxygen therapy. We recorded 135 (11.6%) deaths within 30 days of diagnosis. We found no association between chronic use of RAAS blockers and mortality (unadjusted HR = 1.13, 95% CI [0.8-1.6]; propensity inverse probability treatment weighted HR = 1.09 [0.86-1.39]; propensity standardized mortality ratio weighted HR = 1.08 [0.79-1.47]). Our comprehensive review of previous studies highlighted that significant associations were mostly found in unrestricted populations with inappropriate adjustment, or with biased in-hospital exposure measurement. CONCLUSION: Our results do not support previous concerns regarding these drugs, nor a potential protective effect as reported in previous poorly designed studies and meta-analyses. RAAS blockers should not be discontinued during the pandemic, while in-hospital management of these drugs will be clarified by randomized trials. NCT04262921.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , COVID-19/mortality , Renin-Angiotensin System/drug effects , Aged , Aged, 80 and over , Cohort Studies , Female , France , Humans , Hypertension , Male , Middle Aged , Pandemics , Propensity Score , Prospective Studies
17.
Cancers (Basel) ; 13(6)2021 Mar 21.
Article in English | MEDLINE | ID: covidwho-1143460

ABSTRACT

(1) Background: Several smaller studies have shown that COVID-19 patients with cancer are at a significantly higher risk of death. Our objective was to compare patients hospitalized for COVID-19 with cancer to those without cancer using national data and to study the effect of cancer on the risk of hospital death and intensive care unit (ICU) admission. (2) Methods: All patients hospitalized in France for COVID-19 in March-April 2020 were included from the French national administrative database, which contains discharge summaries for all hospital admissions in France. Cancer patients were identified within this population. The effect of cancer was estimated with logistic regression, adjusting for age, sex and comorbidities. (3) Results: Among the 89,530 COVID-19 patients, we identified 6201 cancer patients (6.9%). These patients were older and were more likely to be men and to have complications (acute respiratory and kidney failure, venous thrombosis, atrial fibrillation) than those without cancer. In patients with hematological cancer, admission to ICU was significantly more frequent (24.8%) than patients without cancer (16.4%) (p < 0.01). Solid cancer patients without metastasis had a significantly higher mortality risk than patients without cancer (aOR = 1.4 [1.3-1.5]), and the difference was even more marked for metastatic solid cancer patients (aOR = 3.6 [3.2-4.0]). Compared to patients with colorectal cancer, patients with lung cancer, digestive cancer (excluding colorectal cancer) and hematological cancer had a higher mortality risk (aOR = 2.0 [1.6-2.6], 1.6 [1.3-2.1] and 1.4 [1.1-1.8], respectively). (4) Conclusions: This study shows that, in France, patients with COVID-19 and cancer have a two-fold risk of death when compared to COVID-19 patients without cancer. We suggest the need to reorganize facilities to prevent the contamination of patients being treated for cancer, similar to what is already being done in some countries.

19.
Eur J Clin Microbiol Infect Dis ; 40(9): 2023-2028, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1122785

ABSTRACT

During an epidemic period, we compared patients hospitalized for initial suspicion of COVID-19 but for whom an alternative diagnosis was finally retained (n = 152) with those who had COVID-19 (n = 222). Most common diagnoses were another infectious disease and heart failure. COVID-19-negative patients were more often active smokers had less often cough, fever, and digestive symptoms, as compared to the 222 COVID-19-positive patients. They had higher median neutrophil and lymphocyte counts and lower CRP level. In multivariate analysis, no current smoking, neurocognitive disorder, myalgia, and fibrinogen ≥4g/L were independently associated with a final diagnosis of COVID-19.


Subject(s)
COVID-19/diagnosis , Adult , Aged , COVID-19/therapy , COVID-19/virology , Hospitalization , Humans , Male , Patients/statistics & numerical data , Retrospective Studies , SARS-CoV-2/physiology
20.
SELECTION OF CITATIONS
SEARCH DETAIL