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1.
J Epidemiol Glob Health ; 12(2): 196-205, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1821089

ABSTRACT

INTRODUCTION: Following the first year of the COVID-19 pandemic, a complete analysis of the characteristics of the deceased hospitalized patients was performed, to identify factors related to premature mortality and to compare patient profiles according to the epidemic periods. METHODS: Retrospective analysis of 1104 deceased patients in two University Hospitals in South-eastern France, between March 1, 2020 and March 12, 2021 from Hospital's electronic medical records was performed. RESULTS: Mean age was 80 years (± 11.1) and 10% of the deceased were younger than 65 years with specific comorbidities, e.g., genetic conditions, metastatic cancer, or massive obesity. Among the three clusters identified, two clusters (75% of deceased patients) include very elderly patients with numerous comorbidities, and differ by their proportion of dependent institutionalized patients. The third cluster is made up of younger patients with fewer but severe comorbidities. Deceased patients' profiles varied according to the epidemic periods: during the first period (March-June 2020), more patients were institutionalized. The second period (September-December2020) coincided with a higher mortality rate. CONCLUSIONS: This study confirmed that most patients hospitalized and dying from COVID-19 were frail, i.e., elderly and/or highly comorbid and that the small proportion of young patients had severe comorbidities.


Subject(s)
COVID-19 , Pandemics , Aged , Aged, 80 and over , COVID-19/epidemiology , Comorbidity , Hospitalization , Humans , Retrospective Studies , SARS-CoV-2
2.
BMJ Open ; 12(4): e057368, 2022 04 22.
Article in English | MEDLINE | ID: covidwho-1807412

ABSTRACT

INTRODUCTION: Prognosis of patients with COVID-19 depends on the severity of the pulmonary affection. The most severe cases may progress to acute respiratory distress syndrome (ARDS), which is associated with a risk of long-term repercussions on respiratory function and neuromuscular outcomes. The functional repercussions of severe forms of COVID-19 may have a major impact on quality of life, and impair the ability to return to work or exercise. Social inequalities in healthcare may influence prognosis, with socially vulnerable individuals more likely to develop severe forms of disease. We describe here the protocol for a prospective, multicentre study that aims to investigate the influence of social vulnerability on functional recovery in patients who were hospitalised in intensive care for ARDS caused by COVID-19. This study will also include an embedded qualitative study that aims to describe facilitators and barriers to compliance with rehabilitation, describe patients' health practices and identify social representations of health, disease and care. METHODS AND ANALYSIS: The "Functional Recovery From Acute Respiratory Distress Syndrome (ARDS) Due to COVID-19: Influence of Socio-Economic Status" (RECOVIDS) study is a mixed-methods, observational, multicentre cohort study performed during the routine follow-up of post-intensive care unit (ICU) functional recovery after ARDS. All patients admitted to a participating ICU for PCR-proven SARS-CoV-2 infection and who underwent chest CT scan at the initial phase AND who received respiratory support (mechanical or not) or high-flow nasal oxygen, AND had ARDS diagnosed by the Berlin criteria will be eligible. The primary outcome is the presence of lung sequelae at 6 months after ICU discharge, defined either by alterations on pulmonary function tests, oxygen desaturation during a standardised 6 min walk test or fibrosis-like pulmonary findings on chest CT. Patients will be considered to be socially disadvantaged if they have an "Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examen de Santé" (EPICES) score ≥30.17 at inclusion. ETHICS AND DISSEMINATION: The study protocol and the informed consent form were approved by an independent ethics committee (Comité de Protection des Personnes Sud Méditerranée II) on 10 July 2020 (2020-A02014-35). All patients will provide informed consent before participation. Findings will be published in peer-reviewed journals and presented at national and international congresses. TRIAL REGISTRATION NUMBER: NCT04556513.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , COVID-19/complications , Cohort Studies , Humans , Oxygen , Prospective Studies , Quality of Life , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , SARS-CoV-2 , Social Class , Treatment Outcome
3.
Front Med (Lausanne) ; 9: 824563, 2022.
Article in English | MEDLINE | ID: covidwho-1785358

ABSTRACT

Background: The optimal isolation time of COVID-19 patients in intensive care unit (ICU) is debated. We investigated the impact of two different COVID-19 patient isolation time strategies on healthcare workers (HCW) contamination, intensity of nursing care and potential associated adverse events. Methods: We prospectively included all consecutive COVID-19 patients and HCW in our ICU in the first two pandemic waves (March to May 2020 and August to November 2020). Specific isolation measures for COVID-19 patients were released after two negative RT-PCR assays in the first wave and 14 days after the onset of symptoms in the second wave. Contamination of HCW was assessed at the end of each pandemic wave by combining both a RT-PCR assay and a serological test. Results: Overall, 117 COVID-19 patients and 73 HCW were included. Despite an earlier release from isolation after ICU admission in the second than in the first wave [6 (4-8) vs. 15 (11-19) days, p < 0.01], the proportion of HCW with a positive serological test (16 vs. 17%, p = 0.94) or with a positive RT-PCR assay (3 vs. 5%, p = 0.58) was not different between the two waves. Although a lower nurse-to-bed ratio, the intensity of nursing care was higher in the second than in the first wave. A longer isolation time was associated with accidental extubation (OR = 1.18, 95%CI:1.07-1.35, p = 0.005) but neither with ventilator-associated pneumonia nor with dysglycemia. Conclusion: A shorter isolation time of COVID-19 patients in ICU was not associated with higher HCW contamination, while a longer isolation time seemed to be associated with higher accidental extubation.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-308833

ABSTRACT

Objectives: The variant 20I/501Y.V1, associated to a higher risk of transmissibility, emerged in Nice city (South East of France, French Riviera) during January 2021. The pandemic has resumed late December 2020 in this aera. A high incidence rate together with a fast turn-over of the main circulating variants, provided us the opportunity to analyze modifications in clinical profile and outcome traits. Methods: : Observational study in the University hospital of Nice from December 2020 to February 2021. We analyzed data of sequencing of SARS-CoV-2 from the sewage collector and PCR screening from all positive samples at the hospital. Then, we described the characteristics of all COVID-19 patients admitted in the emergency department (ED) (n=1247) and those hospitalized in the infectious diseases ward or ICU (n=232). Results: : the UK-variant was absent in this area in December, then increasingly spread in January representing 59% of the PCR screening performed mid-February. The rate of patients over 65 years admitted to the ED decreased from 63% to 50% (p=0.001). The mean age of hospitalized patients in the infectious diseases ward decreased from 70.7 to 59.2 (p<0.001) while the proportion of patients without comorbidity increased from 16% to 42% (p=0.007). Conclusion: Spread of the UK-variant in the South East of France affects younger and healthier patients.

5.
SSRN;
Preprint in English | SSRN | ID: ppcovidwho-325830

ABSTRACT

Background: Severe COVID-19 is associated with exaggerated complement activation. We assessed the efficacy and safety of avdoralimab (an anti-C5aR1 mAb) in severe COVID-19. Methods: FORCE was a double-blind, placebo-controlled study. Patients receiving oxygen support ≥5 L/min to maintain SpO2 > 93% (WHO scale ≥ 5) were randomly assigned, in a 1:1 ratio to the avdoralimab and placebo arms. Avdoralimab (500 mg loading dose followed by a 200 mg maintenance dose) or placebo (normal saline) was administered intravenously every 48 h until oxygen therapy was no longer needed, and for a maximum of 14 days. Patients received conventional oxygen therapy or high-flow oxygen (HFO)/non-invasive ventilation (NIV) in cohort 1;HFO, NIV or invasive mechanical ventilation (IMV) in cohort 2 and IMV in cohort 3. The primary outcome was clinical status on the WHO ordinal scale at days 14 and 28 for cohorts 1 and 3, and the number of ventilator-free days at day 28 (VFD28) for cohort 2. Findings: Between May 2020 and January 2021, we randomized 207 patients: 99 in cohort 1, 49 in cohort 2 and 59 in cohort 3. Glucocorticoids were administered to 95% of patients during hospitalization. Avdoralimab did not improve WHO clinical scale score on days 14 and 28 (between-group difference on day 28 of -0.26 (95% CI, -1.2 to 0.7, p =0.7) in cohort 1 and -0.28 (95% CI, -1.8 to 1.2, p =0.6) in cohort 3). Avdoralimab did not improve VFD28 in cohort 2 (between-group difference of -6.3 (95% CI, -13.2 to 0.7, p =0.96), or secondary outcomes in any cohort. No subgroup of interest was identified. Interpretation: In this randomized trial in hospitalized patients with severe COVID-19 pneumonia, avdoralimab did not significantly improve clinical status at days 14 or 28.

6.
Lancet Respir Med ; 9(12): 1387-1395, 2021 12.
Article in English | MEDLINE | ID: covidwho-1621129

ABSTRACT

BACKGROUND: Awake prone positioning has been reported to improve oxygenation for patients with COVID-19 in retrospective and observational studies, but whether it improves patient-centred outcomes is unknown. We aimed to evaluate the efficacy of awake prone positioning to prevent intubation or death in patients with severe COVID-19 in a large-scale randomised trial. METHODS: In this prospective, a priori set up and defined, collaborative meta-trial of six randomised controlled open-label superiority trials, adults who required respiratory support with high-flow nasal cannula for acute hypoxaemic respiratory failure due to COVID-19 were randomly assigned to awake prone positioning or standard care. Hospitals from six countries were involved: Canada, France, Ireland, Mexico, USA, Spain. Patients or their care providers were not masked to allocated treatment. The primary composite outcome was treatment failure, defined as the proportion of patients intubated or dying within 28 days of enrolment. The six trials are registered with ClinicalTrials.gov, NCT04325906, NCT04347941, NCT04358939, NCT04395144, NCT04391140, and NCT04477655. FINDINGS: Between April 2, 2020 and Jan 26, 2021, 1126 patients were enrolled and randomly assigned to awake prone positioning (n=567) or standard care (n=559). 1121 patients (excluding five who withdrew from the study) were included in the intention-to-treat analysis. Treatment failure occurred in 223 (40%) of 564 patients assigned to awake prone positioning and in 257 (46%) of 557 patients assigned to standard care (relative risk 0·86 [95% CI 0·75-0·98]). The hazard ratio (HR) for intubation was 0·75 (0·62-0·91), and the HR for mortality was 0·87 (0·68-1·11) with awake prone positioning compared with standard care within 28 days of enrolment. The incidence of prespecified adverse events was low and similar in both groups. INTERPRETATION: Awake prone positioning of patients with hypoxaemic respiratory failure due to COVID-19 reduces the incidence of treatment failure and the need for intubation without any signal of harm. These results support routine awake prone positioning of patients with COVID-19 who require support with high-flow nasal cannula. FUNDING: Open AI inc, Rice Foundation, Projet Hospitalier de Recherche Clinique Interrégional, Appel d'Offre 2020, Groupement Interrégional de Recherche Clinique et d'Innovation Grand Ouest, Association pour la Promotion à Tours de la Réanimation Médicale, Fond de dotation du CHRU de Tours, Fisher & Paykel Healthcare Ltd.


Subject(s)
COVID-19 , Patient Positioning , Prone Position , Respiratory Insufficiency , Adult , COVID-19/therapy , Canada , France , Humans , Ireland , Mexico , Prospective Studies , Respiratory Insufficiency/therapy , SARS-CoV-2 , Spain , Treatment Outcome , United States , Wakefulness
7.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-294524

ABSTRACT

Objectives The variant 20I/501Y.V1, associated to a higher risk of transmissibility, emerged in Nice city (South East of France, French Riviera) during January 2021. The pandemic has resumed late December 2020 in this aera. A high incidence rate together with a fast turn-over of the main circulating variants, provided us the opportunity to analyze modifications in clinical profile and outcome traits. Methods Observational study in the University hospital of Nice from December 2020 to February 2021. We analyzed data of sequencing of SARS-CoV-2 from the sewage collector and PCR screening from all positive samples at the hospital. Then, we described the characteristics of all COVID-19 patients admitted in the emergency department (ED) (n=1247) and those hospitalized in the infectious diseases ward or ICU (n=232). Demographic data, clinical signs and severity were recorded by the NEWS-2, SAPS-2 and SOFA scores were recorded and analyzed. Results the UK-variant was absent in the area in December, then increasingly spread in January representing 59% of the PCR screening performed mid-February. The rate of patients over 65 years admitted to the ED decreased from 63% to 50% (p=0.001). The mean age of hospitalized patients in the infectious diseases ward decreased from 70.7 to 59.2 (p<0.001) while the proportion of patients without comorbidity increased from 16% to 42% (p=0.007). Neither the NEWS-2 score nor the main signs of clinical severity have changed over time. Conclusion Spread of the UK-variant in the South East of France affects younger and healthier patients.

8.
Clin Microbiol Infect ; 28(1): 114-123, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1474452

ABSTRACT

OBJECTIVES: Initial studies of individuals with coronavirus disease 2019 (COVID-19) revealed that obesity, diabetes and hypertension were associated with severe outcomes. Subsequently, some authors showed that the risk could vary according to age, gender, co-morbidities and medical history. In a nationwide retrospective cohort, we studied the association between these co-morbidities and patients' requirement for invasive mechanical ventilation (IMV) or their death. METHODS: All French adult inpatients with COVID-19 admitted during the first epidemic wave (February to September 2020) were included. When patients were diagnosed with obesity, diabetes or hypertension for the first time in 2020, these conditions were considered as incident co-morbidities, otherwise they were considered prevalent. We compared outcomes of IMV and in-hospital death according to obesity, diabetes and hypertension, taking age, gender and Charlson's co-morbidity index score (CCIS) into account. RESULTS: A total of 134 209 adult inpatients with COVID-19 were included, half of them had hypertension (n = 66 613, 49.6%), one in four were diabetic (n = 32 209, 24.0%), and one in four were obese (n = 32 070, 23.9%). Among this cohort, IMV was required for 13 596 inpatients, and 19 969 patients died. IMV and death were more frequent in male patients (adjusted oods ratio (aOR) 2.0, 95% CI 1.9-2.1 and aOR 1.5, 95% CI 1.4-1.5, respectively), IMV in patients with co-morbidities (aOR 2.1, 95% CI 2.0-2.2 for CCIS = 2 and aOR 3.0, 95% CI 2.8-3.1 for CCIS ≥5), and death in patients aged 80 or above (aOR 17.0, 95% CI 15.5-18.6). Adjusted on age, gender and CCIS, death was more frequent among inpatients with obesity (aOR 1.2, 95% CI 1.1-1.2) and diabetes (aOR 1.2, 95% CI 1.1-1.2). IMV was more frequently necessary for inpatients with obesity (aOR 1.9, 95% CI 1.8-2.0), diabetes (aOR 1.4, 95% CI 1.3-1.4) and hypertension (aOR 1.7, 95% CI 1.6-1.8). Comparatively, IMV was more often required for patients with the following incident co-morbidities: obesity (aOR 3.5, 95% CI 3.3-3.7), diabetes (aOR 2.0, 95% CI 1.8-2.1) and hypertension (aOR 2.5, 95% CI 2.4-2.6). CONCLUSIONS: Among 134 209 inpatients with COVID-19, mortality was more frequent among patients with obesity and diabetes. IMV was more frequently necessary for inpatients with obesity, diabetes and hypertension. Patients for whom these were incident co-morbidities were particularly at risk. Specific medical monitoring and vaccination should be priorities for patients with these co-morbidities.


Subject(s)
COVID-19/mortality , Diabetes Mellitus , Hypertension , Obesity , Adolescent , Adult , Aged , Aged, 80 and over , Comorbidity , Diabetes Mellitus/epidemiology , Female , Hospital Mortality , Humans , Hypertension/epidemiology , Inpatients , Male , Middle Aged , Obesity/complications , Obesity/epidemiology , Respiration, Artificial , Retrospective Studies , Risk Factors , Young Adult
9.
Sci Rep ; 11(1): 18456, 2021 09 16.
Article in English | MEDLINE | ID: covidwho-1415951

ABSTRACT

The variant 20I/501Y.V1, associated to a higher risk of transmissibility, emerged in Nice city (Southeast of France, French Riviera) during January 2021. The pandemic has resumed late December 2020 in this area. A high incidence rate together with a fast turn-over of the main circulating variants, provided us the opportunity to analyze modifications in clinical profile and outcome traits. We performed an observational study in the University hospital of Nice from December 2020 to February 2021. We analyzed data of sequencing of SARS-CoV-2 from the sewage collector and PCR screening from all positive samples at the hospital. Then, we described the characteristics of all COVID-19 patients admitted in the emergency department (ED) (n = 1247) and those hospitalized in the infectious diseases ward or ICU (n = 232). The UK-variant was absent in this area in December, then increasingly spread in January representing 59% of the PCR screening performed mid-February. The rate of patients over 65 years admitted to the ED decreased from 63 to 50% (p = 0.001). The mean age of hospitalized patients in the infectious diseases ward decreased from 70.7 to 59.2 (p < 0.001) while the proportion of patients without comorbidity increased from 16 to 42% (p = 0.007). Spread of the UK-variant in the Southeast of France affects younger and healthier patients.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/epidemiology , SARS-CoV-2/genetics , Sewage/virology , Age Factors , Aged , Aged, 80 and over , COVID-19/virology , Comorbidity , Female , France/epidemiology , Hospitalization/statistics & numerical data , Hospitals, University , Humans , Incidence , Male , Middle Aged , United Kingdom/epidemiology , Wastewater-Based Epidemiological Monitoring
10.
Ann Intensive Care ; 11(1): 90, 2021 Jun 04.
Article in English | MEDLINE | ID: covidwho-1255966

ABSTRACT

BACKGROUND: We investigated the impact of the COVID-19 crisis on mental health of professionals working in the intensive care unit (ICU) according to the intensity of the epidemic in France. METHODS: This cross-sectional survey was conducted in 77 French hospitals from April 22 to May 13 2020. All ICU frontline healthcare workers were eligible. The primary endpoint was the mental health, assessed using the 12-item General Health Questionnaire. Sources of stress during the crisis were assessed using the Perceived Stressors in Intensive Care Units (PS-ICU) scale. Epidemic intensity was defined as high or low for each region based on publicly available data from Santé Publique France. Effects were assessed using linear mixed models, moderation and mediation analyses. RESULTS: In total, 2643 health professionals participated; 64.36% in high-intensity zones. Professionals in areas with greater epidemic intensity were at higher risk of mental health issues (p < 0.001), and higher levels of overall perceived stress (p < 0.001), compared to low-intensity zones. Factors associated with higher overall perceived stress were female sex (B = 0.13; 95% confidence interval [CI] = 0.08-0.17), having a relative at risk of COVID-19 (B = 0.14; 95%-CI = 0.09-0.18) and working in high-intensity zones (B = 0.11; 95%-CI = 0.02-0.20). Perceived stress mediated the impact of the crisis context on mental health (B = 0.23, 95%-CI = 0.05, 0.41) and the impact of stress on mental health was moderated by positive thinking, b = - 0.32, 95% CI = - 0.54, - 0.11. CONCLUSION: COVID-19 negatively impacted the mental health of ICU professionals. Professionals working in zones where the epidemic was of high intensity were significantly more affected, with higher levels of perceived stress. This study is supported by a grant from the French Ministry of Health (PHRC-COVID 2020).

11.
Ann Intensive Care ; 11(1): 87, 2021 May 31.
Article in English | MEDLINE | ID: covidwho-1247600

ABSTRACT

BACKGROUND: Dexamethasone decreases mortality in patients with severe coronavirus disease 2019 (COVID-19) and has become the standard of care during the second wave of pandemic. Dexamethasone is an immunosuppressive treatment potentially increasing the risk of secondary hospital acquired infections in critically ill patients. We conducted an observational retrospective study in three French intensive care units (ICUs) comparing the first and second waves of pandemic to investigate the role of dexamethasone in the occurrence of ventilator-associated pneumonia (VAP) and blood stream infections (BSI). Patients admitted from March to November 2020 with a documented COVID-19 and requiring mechanical ventilation (MV) for ≥ 48 h were included. The main study outcomes were the incidence of VAP and BSI according to the use of dexamethasone. Secondary outcomes were the ventilator-free days (VFD) at day-28 and day-60, ICU and hospital length of stay and mortality. RESULTS: Among the 151 patients included, 84 received dexamethasone, all but one during the second wave. VAP occurred in 63% of patients treated with dexamethasone (DEXA+) and 57% in those not receiving dexamethasone (DEXA-) (p = 0.43). The cumulative incidence of VAP, considering death, duration of MV and late immunosuppression as competing factors was not different between groups (p = 0.59). A multivariate analysis did not identify dexamethasone as an independent risk factor for VAP occurrence. The occurrence of BSI was not different between groups (29 vs. 30%; p = 0.86). DEXA+ patients had more VFD at day-28 (9 (0-21) vs. 0 (0-11) days; p = 0.009) and a reduced ICU length of stay (20 (11-44) vs. 32 (17-46) days; p = 0.01). Mortality did not differ between groups. CONCLUSIONS: In this cohort of COVID-19 patients requiring invasive MV, dexamethasone was not associated with an increased incidence of VAP or BSI. Dexamethasone might not explain the high rates of VAP and BSI observed in critically ill COVID-19 patients.

12.
Front Physiol ; 12: 611772, 2021.
Article in English | MEDLINE | ID: covidwho-1154242

ABSTRACT

BACKGROUND: Renal involvement in syndrome coronavirus 2 (SARS-CoV-2) infection has been retrospectively described, especially acute kidney injury (AKI). However, quantitative proteinuria assessment and its implication in coronavirus disease 2019 (COVID-19) remain unknown. METHODS: In this prospective, multicenter study in France, we collected clinical and biological data including urinary protein to creatine ratio (UPCR) in patients presenting with moderate to severe COVID-19. Clinical outcome was analyzed according to the level of UPCR. RESULTS: 42/45 patients (93.3%) had renal involvement (abnormal urinary sediment and/or AKI). Significant proteinuria occurred in 60% of patients. Urine protein electrophoresis showed tubular protein excretion in 83.8% of patients with proteinuria. Inflammatory parametersand D-dimer concentrations correlated with proteinuria level. Patients who required intensive care unit (ICU) admission had higher proteinuria (p = 0.008). On multivariate analysis, proteinuria greater than 0.3 g/g was related to a higher prevalence of ICU admission [OR = 4.72, IC95 (1.16-23.21), p = 0.03], acute respiratory distress syndrome (ARDS) [OR = 6.89, IC95 (1.41-53.01, p = 0.02)], nosocomial infections [OR = 3.75, IC95 (1.11-13.55), p = 0.03], longer inpatient hospital stay (p = 0.003). CONCLUSION: Renal involvement is common in moderate to severe SARS-CoV-2 infection. Proteinuria at baseline is an independent risk factor for increased hospitalization duration and ICU admission in patients with COVID-19.

13.
Blood Adv ; 5(5): 1523-1534, 2021 03 09.
Article in English | MEDLINE | ID: covidwho-1121096

ABSTRACT

Dysregulated immune response is the key factor leading to unfavorable coronavirus disease 2019 (COVID-19) outcome. Depending on the pathogen-associated molecular pattern, the NLRP3 inflammasome can play a crucial role during innate immunity activation. To date, studies describing the NLRP3 response during severe acute respiratory syndrome coronavirus 2 infection in patients are lacking. We prospectively monitored caspase-1 activation levels in peripheral myeloid cells from healthy donors and patients with mild to critical COVID-19. The caspase-1 activation potential in response to NLRP3 inflammasome stimulation was opposed between nonclassical monocytes and CD66b+CD16dim granulocytes in severe and critical COVID-19 patients. Unexpectedly, the CD66b+CD16dim granulocytes had decreased nigericin-triggered caspase-1 activation potential associated with an increased percentage of NLRP3 inflammasome impaired immature neutrophils and a loss of eosinophils in the blood. In patients who recovered from COVID-19, nigericin-triggered caspase-1 activation potential in CD66b+CD16dim cells was restored and the proportion of immature neutrophils was similar to control. Here, we reveal that NLRP3 inflammasome activation potential differs among myeloid cells and could be used as a biomarker of a COVID-19 patient's evolution. This assay could be a useful tool to predict patient outcome. This trial was registered at www.clinicaltrials.gov as #NCT04385017.


Subject(s)
COVID-19/blood , Inflammasomes/metabolism , Myeloid Cells/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/immunology , Biomarkers/blood , COVID-19/immunology , Case-Control Studies , Humans , Inflammasomes/blood , Middle Aged , Prospective Studies , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
14.
Front Med (Lausanne) ; 7: 603961, 2020.
Article in English | MEDLINE | ID: covidwho-1083700

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged in Wuhan in December 2019 and has since spread across the world. Even though the majority of patients remain completely asymptomatic, some develop severe systemic complications. In this prospective study we compared the immunological profile of 101 COVID-19 patients with either mild, moderate or severe form of the disease according to the WHO classification, as well as of 50 healthy subjects, in order to identify functional immune factors independently associated with severe forms of COVID-19. Plasma cytokine levels, and cytokine levels upon in vitro non-specific stimulation of innate and adaptive immune cells, were measured at several time points during the course of the disease. As described previously, inflammatory cytokines IL1ß, IL6, IL8, and TNFα associated with cytokine storm were significantly increased in the plasma of moderate and severe COVID-19 patients (p < 0.0001 for all cytokines). During follow-up, plasma IL6 levels decreased between the moment of admission to the hospital and at the last observation carried forward for patients with favorable outcome (p = 0.02148). After in vitro stimulation of immune cells from COVID-19 patients, reduced levels of both type I and type II interferons (IFNs) upon in vitro stimulation were correlated with increased disease severity [type I IFN (IFNα): p > 0.0001 mild vs. moderate and severe; type II IFN (IFNγ): p = 0.0002 mild vs. moderate and p < 0.0001 mild vs. severe] suggesting a functional exhaustion of IFNs production. Stimulated IFNα levels lower than 2.1 pg/ml and IFNγ levels lower than 15 IU/mL at admission to the hospital were associated with more complications during hospitalization (p = 0.0098 and p =0.0002, respectively). A low IFNγ level was also confirmed by multivariable analysis [p = 0.0349 OR = 0.98 (0.962; 0.999)] as an independent factor of complications. In vitro treatment with type IFNα restored type IFNγ secretion in COVID-19 patients while the secretion of pro-inflammatory cytokines IL6 and IL1ß remained stable or decreased, respectively. These results (a) demonstrate a functional exhaustion of both innate and adaptive immune response in severe forms of COVID-19; (b) identify IFNα and IFNγ as new potential biomarkers of severity; and (c) highlight the importance of targeting IFNs when considering COVID-19 treatment in order to re-establish a normal balance between inflammatory and Th1 effector cytokines.

15.
Front Med (Lausanne) ; 7: 608804, 2020.
Article in English | MEDLINE | ID: covidwho-1081183

ABSTRACT

Frontline health care workers (HCWs) have been particularly exposed to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) since the start of the pandemic but the clinical features and immune responses of those infected with SARS-CoV-2 have not been well described. In a prospective single center cohort study, we enrolled 196 frontline HCWs exposed to the SARS-Cov-2 and 60 patients with moderate and severe forms of the coronavirus disease 2019 (COVID-19). Serological tests and cytokines assay were performed to analyze SARS-CoV-2-specific humoral and cellular immunity. Of the 196 HCWs tested, 15% had specific antibodies against SARS-CoV-2 and 45% of seropositive HCWs were strictly asymptomatic. However, in comparison to moderate and severe forms, HCWs with mild or asymptomatic forms of COVID-19 showed lower specific IgA and IgG peaks, consistent with their mild symptoms, and a robust immune cellular response, illustrated by a high production of type I and II interferons. Further studies are needed to evaluate whether this interferon functional immune assay, routinely applicable, can be useful in predicting the risk of severe forms of COVID-19.

16.
JAMA Dermatol ; 157(2): 202-206, 2021 02 01.
Article in English | MEDLINE | ID: covidwho-959045

ABSTRACT

Importance: Chilblain-like lesions have been reported during the coronavirus 2019 (COVID-19) pandemic. The pathophysiology of such manifestations remains largely unknown. Objective: To perform a systematic clinical, histologic, and biologic assessment in a cohort of patients with chilblain-like lesions occurring during the COVID-19 pandemic. Design, Setting, and Participants: In this prospective case series carried out with a COVID-19 multidisciplinary consultation group at the University Hospital of Nice, France, 40 consecutive patients presenting with chilblain-like lesions were included. Main Outcomes and Measures: Patients underwent a thorough general and dermatologic examination, including skin biopsies, vascular investigations, biologic analyses, interferon-alpha (IFN-α) stimulation and detection, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) and serologic analysis. Results: Overall, 40 consecutive patients with chilblain-like lesions were included. Most patients were young, with a median (range) age of 22 (12-67) years; 19 were male and 21 were female. The clinical presentation was highly reproducible with chilblain-like lesions mostly on the toes. Bullous and necrotic evolution was observed in 11 patients. Acrocyanosis or cold toes were reported in 19 (47.5%) cases. Criteria compatible with COVID-19 cases were noted in 11 (27.5%) within 6 weeks prior to the eruption. The real-time PCR (rt-PCR) testing results were negative in all cases. Overall, SARS-CoV-2 serology results were positive in 12 patients (30%). D-dimer concentration levels were elevated in 24 (60.0%) cases. Cryoglobulinemia and parvovirus B19 serologic results were negative for all tested patients. The major histologic findings were features of lymphocytic inflammation and vascular damage with thickening of venule walls and pericyte hyperplasia. A significant increase of IFN-α production after in vitro stimulation was observed in the chilblain population compared with patients with mild-severe acute COVID-19. Conclusions and Relevance: Taken together, our results suggest that chilblain-like lesions observed during the COVID-19 pandemic represent manifestations of a viral-induced type I interferonopathy. Trial Registration: ClinicalTrials.gov Identifier: NCT04344119.


Subject(s)
COVID-19/complications , Chilblains/etiology , Adolescent , Adult , Aged , COVID-19/immunology , Chilblains/immunology , Child , Female , Humans , Interferon-alpha/immunology , Male , Middle Aged , Prospective Studies , Young Adult
17.
Chest ; 159(5): 1974-1985, 2021 05.
Article in English | MEDLINE | ID: covidwho-950087

ABSTRACT

BACKGROUND: Cardiac injury has been reported in up to 30% of coronavirus disease 2019 (COVID-19) patients. However, cardiac injury is defined mainly by troponin elevation without description of associated structural abnormalities and its time course has not been studied. RESEARCH QUESTION: What are the ECG and echocardiographic abnormalities as well as their time course in critically ill COVID-19 patients? STUDY DESIGN AND METHODS: The cardiac function of 43 consecutive COVID-19 patients admitted to two ICUs was assessed prospectively and repeatedly, combining ECG, cardiac biomarker, and transthoracic echocardiographic analyses from ICU admission to ICU discharge or death or to a maximum follow-up of 14 days. Cardiac injury was defined by troponin elevation and newly diagnosed ECG or echocardiographic abnormalities, or both. RESULTS: At baseline, 49% of patients demonstrated a cardiac injury, and 70% of patients experienced cardiac injury within the first 14 days of ICU stay, with a median time of occurrence of 3 days (range, 0-7 days). The most frequent abnormalities were ECG or echocardiographic signs, or both, of left ventricular (LV) abnormalities (87% of patients with cardiac injury), right ventricular (RV) systolic dysfunction (47%), pericardial effusion (43%), new-onset atrial arrhythmias (33%), LV relaxation impairment (33%), and LV systolic dysfunction (13%). Between baseline and day 14, the incidence of pericardial effusion and of new-onset atrial arrhythmias increased and the incidence of ECG or echocardiographic signs, or both, of LV abnormalities as well as the incidence of LV relaxation impairment remained stable, whereas the incidence of RV and LV systolic dysfunction decreased. INTERPRETATION: Cardiac injury is common and early in critically ill COVID-19 patients. ECG or echocardiographic signs, or both, of LV abnormalities were the most frequent abnormalities, and patients with cardiac injury experienced more RV than LV systolic dysfunction.


Subject(s)
COVID-19 , Echocardiography/methods , Electrocardiography/methods , Heart Diseases , Troponin/blood , Ventricular Dysfunction, Left , Biomarkers/blood , COVID-19/complications , COVID-19/epidemiology , COVID-19/physiopathology , COVID-19/therapy , Critical Illness/epidemiology , Critical Illness/therapy , Female , France/epidemiology , Heart Diseases/blood , Heart Diseases/diagnosis , Heart Diseases/epidemiology , Heart Diseases/etiology , Humans , Incidence , Intensive Care Units/statistics & numerical data , Male , Middle Aged , SARS-CoV-2 , Ventricular Dysfunction, Left/diagnosis , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/physiopathology
18.
J Am Heart Assoc ; 9(21): e017773, 2020 11 03.
Article in English | MEDLINE | ID: covidwho-889990

ABSTRACT

Background Recent literature reports a strong thrombotic tendency in patients hospitalized for a coronavirus disease 2019 (COVID-19) infection. This characteristic is unusual and seems specific to COVID-19 infections, especially in their severe form. Viral infections can trigger acquired thrombophilia, which can then lead to thrombotic complications. We investigate for the presence of acquired thrombophilia, which could participate in this phenomenon, and report its prevalence. We also wonder if these thrombophilias participate in the bad prognosis of severe COVID-19 infections. Methods and Results In 89 consecutive patients hospitalized for COVID-19 infection, we found a 20% prevalence of PS (protein S) deficiency and a high (ie, 72%) prevalence of antiphospholipid antibodies: mainly lupus anticoagulant. The presence of PS deficiency or antiphospholipid antibodies was not linked with a prolonged activated partial thromboplastin time nor with D-dimer, fibrinogen, or CRP (C-reactive protein) concentrations. These coagulation abnormalities are also not linked with thrombotic clinical events occurring during hospitalization nor with mortality. Conclusions We assess a high prevalence of positive tests detecting thrombophilia in COVID-19 infections. However, in our series, these acquired thrombophilias are not correlated with the severity of the disease nor with the occurrence of thrombotic events. Albeit the strong thrombotic tendency in COVID-19 infections, the presence of frequent acquired thrombophilia may be part of the inflammation storm of COVID-19 and should not systematically modify our strategy on prophylactic anticoagulant treatment, which is already revised upwards in this pathological condition. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT04335162.


Subject(s)
Antiphospholipid Syndrome/epidemiology , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Protein S Deficiency/epidemiology , Thrombosis/epidemiology , Aged , Antibodies, Antiphospholipid/blood , Antiphospholipid Syndrome/blood , Antiphospholipid Syndrome/diagnosis , Biomarkers/blood , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Female , France/epidemiology , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Prevalence , Prognosis , Protein S/analysis , Protein S Deficiency/blood , Protein S Deficiency/diagnosis , Risk Factors , Severity of Illness Index , Thrombosis/blood , Thrombosis/diagnosis
20.
Clin Pharmacol Ther ; 108(5): 1090-1097, 2020 11.
Article in English | MEDLINE | ID: covidwho-615066

ABSTRACT

Association between Hydroxychloroquine (HCQ) and Azithromycin (AZT) is under evaluation for patients with lower respiratory tract infection (LRTI) caused by the Severe Acute Respiratory Syndrome (SARS-CoV-2). Both drugs have a known torsadogenic potential, but sparse data are available concerning QT prolongation induced by this association. Our objective was to assess for COVID-19 LRTI variations of QT interval under HCQ/AZT in patients hospitalized, and to compare manual versus automated QT measurements. Before therapy initiation, a baseline 12 lead-ECG was electronically sent to our cardiology department for automated and manual QT analysis (Bazett and Fridericia's correction), repeated 2 days after initiation. According to our institutional protocol (Pasteur University Hospital), HCQ/AZT was initiated only if baseline QTc ≤ 480ms and potassium level> 4.0 mmol/L. From March 24th to April 20th 2020, 73 patients were included (mean age 62 ± 14 years, male 67%). Two patients out of 73 (2.7%) were not eligible for drug initiation (QTc ≥ 500 ms). Baseline average automated QTc was 415 ± 29 ms and lengthened to 438 ± 40 ms after 48 hours of combined therapy. The treatment had to be stopped because of significant QTc prolongation in two out of 71 patients (2.8%). No drug-induced life-threatening arrhythmia, nor death was observed. Automated QTc measurements revealed accurate in comparison with manual QTc measurements. In this specific population of inpatients with COVID-19 LRTI, HCQ/AZT could not be initiated or had to be interrupted in less than 6% of the cases.


Subject(s)
Azithromycin , Coronavirus Infections , Drug Monitoring , Electrocardiography/methods , Hydroxychloroquine , Long QT Syndrome , Pandemics , Pneumonia, Viral/drug therapy , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/adverse effects , Anti-Infective Agents/pharmacokinetics , Azithromycin/administration & dosage , Azithromycin/adverse effects , Azithromycin/pharmacokinetics , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/physiopathology , Dimensional Measurement Accuracy , Drug Monitoring/instrumentation , Drug Monitoring/methods , Drug Monitoring/standards , Female , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Hydroxychloroquine/pharmacokinetics , Long QT Syndrome/chemically induced , Long QT Syndrome/diagnosis , Male , Middle Aged , Outcome Assessment, Health Care , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , SARS-CoV-2 , Torsades de Pointes/chemically induced , Torsades de Pointes/prevention & control
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