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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-320240

ABSTRACT

Introduction: Although early identified as a deadly infectious disease, the precise mortality rate of the most severe forms of COVID-19 is a matter of debate. To the best of our knowledge, no study investigated so far, the causes that ultimately led to death as well as the relation between timing and causes of death. Material: & Methods: We performed a retrospective study in eight ICU within eight French hospitals. All consecutive adult patients (aged≥ 18 years old) admitted in the ICU with a PCR-confirmed SARS-CoV-2 infection and acute respiratory failure were included in the analysis. Causes and timing of death were reported based on medical records. A binomial logistic regression statistical analysis was performed to identify the determinants associated with ICU-mortality. Results: : From March 1 st, 2020 to April 28 th , 287 patients were admitted to ICU for SARS-CoV-2 related acute respiratory failure. COVID-19 related multiple organ dysfunction syndromes (MODS) was the leading cause of death (29%, n=27/93). End-of-life decisions occurred in 25% of patients (n=23/93). Secondary infections-related MODS accounted for 21% of ICU death, with a majority of ventilator-associated pneumonia. Fatal ischemic events (venous or arterial) occurred in 12% of patients. Refractory hypoxemia was a relatively uncommon cause of death and occurred only in 8 cases (9%). Regarding the timing of death, only one death occurred during the first three days of ICU admission. Determinants associated with ICU-mortality in logistic regression were age >65, requirement for vasopressors, renal replacement therapy and extracorporeal membrane oxygenation. Conclusion: Our data suggest the existence of a specific pattern of outcome in severe COVID-19 patients compared to severe bacterial and viral pneumonia, consisting in a high proportion of delayed COVID-19 related MODS.

3.
Crit Care ; 25(1): 224, 2021 06 30.
Article in English | MEDLINE | ID: covidwho-1286832

ABSTRACT

BACKGROUND: Previous studies reporting the causes of death in patients with severe COVID-19 have provided conflicting results. The objective of this study was to describe the causes and timing of death in patients with severe COVID-19 admitted to the intensive care unit (ICU). METHODS: We performed a retrospective study in eight ICUs across seven French hospitals. All consecutive adult patients (aged ≥ 18 years) admitted to the ICU with PCR-confirmed SARS-CoV-2 infection and acute respiratory failure were included in the analysis. The causes and timing of ICU deaths were reported based on medical records. RESULTS: From March 1, 2020, to April 28, 287 patients were admitted to the ICU for SARS-CoV-2 related acute respiratory failure. Among them, 93 patients died in the ICU (32%). COVID-19-related multiple organ dysfunction syndrome (MODS) was the leading cause of death (37%). Secondary infection-related MODS accounted for 26% of ICU deaths, with a majority of ventilator-associated pneumonia. Refractory hypoxemia/pulmonary fibrosis was responsible for death in 19% of the cases. Fatal ischemic events (venous or arterial) occurred in 13% of the cases. The median time from ICU admission to death was 15 days (25th-75th IQR, 7-27 days). COVID-19-related MODS had a median time from ICU admission to death of 14 days (25th-75th IQR: 7-19 days), while only one death had occurred during the first 3 days since ICU admission. CONCLUSIONS: In our multicenter observational study, COVID-19-related MODS and secondary infections were the two leading causes of death, among severe COVID-19 patients admitted to the ICU.


Subject(s)
COVID-19/mortality , Multiple Organ Failure/mortality , Pneumonia, Viral/mortality , Adult , Cause of Death , Female , Hospital Mortality , Humans , Hypoxia/mortality , Hypoxia/virology , Intensive Care Units , Ischemia/mortality , Ischemia/virology , Male , Multiple Organ Failure/virology , Pneumonia, Ventilator-Associated/mortality , Pneumonia, Ventilator-Associated/virology , Pneumonia, Viral/virology , Pulmonary Fibrosis/mortality , Pulmonary Fibrosis/virology , Retrospective Studies , SARS-CoV-2
4.
BMJ Open ; 11(5): e045041, 2021 05 11.
Article in English | MEDLINE | ID: covidwho-1259009

ABSTRACT

INTRODUCTION: International guidelines include early nutritional support (≤48 hour after admission), 20-25 kcal/kg/day, and 1.2-2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets. METHODS AND ANALYSIS: NUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2-0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0-1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes. ETHICS AND DISSEMINATION: The NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03573739.


Subject(s)
COVID-19 , Diet, Protein-Restricted , Adult , Critical Illness , Humans , Respiration, Artificial , SARS-CoV-2
5.
Chest ; 159(6): 2309-2317, 2021 06.
Article in English | MEDLINE | ID: covidwho-1064065

ABSTRACT

BACKGROUND: Patients with obesity are at higher risk for community-acquired and nosocomial infections. However, no study has specifically evaluated the relationship between obesity and ventilator-associated pneumonia (VAP). RESEARCH QUESTION: Is obesity associated with an increased incidence of VAP? STUDY DESIGN AND METHODS: This study was a post hoc analysis of the Impact of Early Enteral vs Parenteral Nutrition on Mortality in Patients Requiring Mechanical Ventilation and Catecholamines (NUTRIREA2) open-label, randomized controlled trial performed in 44 French ICUs. Adults receiving invasive mechanical ventilation and vasopressor support for shock and parenteral nutrition or enteral nutrition were included. Obesity was defined as BMI ≥ 30 kg/m2 at ICU admission. VAP diagnosis was adjudicated by an independent blinded committee, based on all available clinical, radiologic, and microbiologic data. Only first VAP episodes were taken into account. Incidence of VAP was analyzed by using the Fine and Gray model, with extubation and death as competing risks. RESULTS: A total of 699 (30%) of the 2,325 included patients had obesity; 224 first VAP episodes were diagnosed (60 and 164 in obese and nonobese groups, respectively). The incidence of VAP at day 28 was 8.6% vs 10.1% in the two groups (hazard ratio, 0.85; 95% CI 0.63-1.14; P = .26). After adjustment on sex, McCabe score, age, antiulcer treatment, and Sequential Organ Failure Assessment at randomization, the incidence of VAP remained nonsignificant between obese and nonobese patients (hazard ratio, 0.893; 95% CI, 0.66-1.2; P = .46). Although no significant difference was found in duration of mechanical ventilation and ICU length of stay, 90-day mortality was significantly lower in obese than in nonobese patients (272 of 692 [39.3%] patients vs 718 of 1,605 [44.7%]; P = .02). In a subgroup of patients (n = 123) with available pepsin and alpha-amylase measurements, no significant difference was found in rate of abundant microaspiration of gastric contents, or oropharyngeal secretions between obese and nonobese patients. INTERPRETATION: Our results suggest that obesity has no significant impact on the incidence of VAP.


Subject(s)
Body Mass Index , Intensive Care Units , Obesity/complications , Pneumonia, Ventilator-Associated/etiology , Respiration, Artificial/adverse effects , Shock/therapy , Aged , Female , France/epidemiology , Humans , Incidence , Male , Middle Aged , Parenteral Nutrition, Total/methods , Pneumonia, Ventilator-Associated/epidemiology , Prevalence , Prognosis , Risk Factors , Survival Rate/trends
6.
Front Med (Lausanne) ; 8: 632933, 2021.
Article in English | MEDLINE | ID: covidwho-1156133

ABSTRACT

Objectives: Different phenotypes have been identified in acute respiratory distress syndrome (ARDS). Existence of several phenotypes in coronavirus disease (COVID-19) related acute respiratory distress syndrome is unknown. We sought to identify different phenotypes of patients with moderate to severe ARDS related to COVID-19. Methods: We conducted an observational study of 416 COVID-19 patients with moderate to severe ARDS at 21 intensive care units in Belgium and France. The primary outcome was day-28 ventilatory free days. Secondary outcomes were mortality on day 28, acute kidney injury, acute cardiac injury, pulmonary embolism, and deep venous thrombosis. Multiple factor analysis and hierarchical classification on principal components were performed to distinguish different clinical phenotypes. Results: We identified three different phenotypes in 150, 176, and 90 patients, respectively. Phenotype 3 was characterized by short evolution, severe hypoxemia, and old comorbid patients. Phenotype 1 was mainly characterized by the absence of comorbidities, relatively high compliance, and long duration of symptoms, whereas phenotype 2 was characterized female sex, and the presence of mild comorbidities such as uncomplicated diabetes or chronic hypertension. The compliance in phenotype 2 was lower than that in phenotype 1, with higher plateau and driving pressure. Phenotype 3 was associated with higher mortality compared to phenotypes 1 and 2. Conclusions: In COVID-19 patients with moderate to severe ARDS, we identified three clinical phenotypes. One of these included older people with comorbidities who had a fulminant course of disease with poor prognosis. Requirement of different treatments and ventilatory strategies for each phenotype needs further investigation.

7.
Crit Care ; 25(1): 106, 2021 03 16.
Article in English | MEDLINE | ID: covidwho-1136238

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice. METHODS: Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ2) test (p < 0·05 was considered as unstable). RESULTS: Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16-24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment. CONCLUSION: Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited. TRIAL REGISTRATION: The study was registered with Clinical trials.gov Identifier: NCT04534569.


Subject(s)
COVID-19/complications , Consensus , Delphi Technique , Respiratory Insufficiency/therapy , Respiratory Insufficiency/virology , Humans
8.
Crit Care ; 25(1): 72, 2021 02 18.
Article in English | MEDLINE | ID: covidwho-1090630

ABSTRACT

BACKGROUND: The COVID-19 pandemic is responsible for many hospitalizations in intensive care units (ICU), with widespread use of invasive mechanical ventilation (IMV) which exposes patients to the risk of ventilator-associated pneumonia (VAP). The characteristics of VAP in COVID-19 patients remain unclear. METHODS: We retrospectively collected data on all patients hospitalized for COVID-19 during the first phase of the epidemic in one of the seven ICUs of the Pays-de-Loire region (North-West France) and who were on invasive mechanical ventilation for more than 48 h. We studied the characteristics of VAP in these patients. VAP was diagnosed based on official recommendations, and we included only cases of VAP that were confirmed by a quantitative microbiological culture. FINDINGS: We analyzed data from 188 patients. Of these patients, 48.9% had VAP and 19.7% experienced multiple episodes. Our study showed an incidence of 39.0 VAP per 1000 days of IMV (until the first VAP episode) and an incidence of 33.7 VAP per 1000 days of IMV (including all 141 episodes of VAP). Multi-microbial VAP accounted for 39.0% of all VAP, and 205 pathogens were identified. Enterobacteria accounted for 49.8% of all the isolated pathogens. Bacteremia was associated in 15 (10.6%) cases of VAP. Pneumonia was complicated by thoracic empyema in five cases (3.5%) and by pulmonary abscess in two cases (1.4%). Males were associated with a higher risk of VAP (sHR 2.24 CI95% [1.18; 4.26] p = 0.013). INTERPRETATION: Our study showed an unusually high incidence of VAP in patients admitted to the ICU for severe COVID-19, even though our services were not inundated during the first wave of the epidemic. We also noted a significant proportion of enterobacteria. VAP-associated complications (abscess, empyema) were not exceptional. REGISTRATION: As an observational study, this study has not been registered.


Subject(s)
COVID-19/therapy , Pneumonia, Ventilator-Associated/epidemiology , Pneumonia, Ventilator-Associated/microbiology , Respiration, Artificial/adverse effects , Aged , COVID-19/epidemiology , Female , France/epidemiology , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged , Retrospective Studies
9.
Crit Care ; 25(1): 52, 2021 02 08.
Article in English | MEDLINE | ID: covidwho-1069579

ABSTRACT

BACKGROUND: Controversies exist on the nature of COVID-19 related acute respiratory distress syndrome (ARDS) in particular on the static compliance of the respiratory system (Crs). We aimed to analyze the association of Crs with outcome in COVID-19-associated ARDS, to ascertain its determinants and to describe its evolution at day-14. METHODS: In this observational multicenter cohort of patients with moderate to severe Covid-19 ARDS, Crs was measured at day-1 and day-14. Association between Crs or Crs/ideal body weight (IBW) and breathing without assistance at day-28 was analyzed with multivariable logistic regression. Determinants were ascertained by multivariable linear regression. Day-14 Crs was compared to day-1 Crs with paired t-test in patients still under controlled mechanical ventilation. RESULTS: The mean Crs in 372 patients was 37.6 ± 13 mL/cmH2O, similar to as in ARDS of other causes. Multivariate linear regression identified chronic hypertension, low PaO2/FiO2 ratio, low PEEP, and low tidal volume as associated with lower Crs/IBW. After adjustment on confounders, nor Crs [OR 1.0 (CI 95% 0.98-1.02)] neither Crs/IBW [OR 0.63 (CI 95% 0.13-3.1)] were associated with the chance of breathing without assistance at day-28 whereas plateau pressure was [OR 0.93 (CI 95% 0.88-0.99)]. In a subset of 108 patients, day-14 Crs decreased compared to day-1 Crs (31.2 ± 14.4 mL/cmH2O vs 37.8 ± 11.4 mL/cmH2O, p < 0.001). The decrease in Crs was not associated with day-28 outcome. CONCLUSION: In a large multicenter cohort of moderate to severe COVID-19 ARDS, mean Crs was decreased below 40 mL/cmH2O and was not associated with day-28 outcome. Crs decreased between day-1 and day-14 but the decrease was not associated with day-28 outcome.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , COVID-19/therapy , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/physiopathology , Respiratory Distress Syndrome/therapy , SARS-CoV-2/pathogenicity , Aged , Cohort Studies , Female , Humans , Male , Middle Aged
10.
Sci Rep ; 11(1): 2388, 2021 01 27.
Article in English | MEDLINE | ID: covidwho-1065954

ABSTRACT

Reverse transcriptase-polymerase chain reaction (RT-PCR) testing is an important tool for diagnosing coronavirus disease 2019 (COVID-19). However, performance concerns have emerged recently, notably regarding sensitivity. We hypothesized that the clinical, biological, and radiological characteristics of patients with a false-negative first RT-PCR test and a final diagnosis of COVID-19 might differ from those of patients with a positive first RT-PCR test. We conducted a multicenter matched case-control study in COVID-19 patients. Patients with a negative first RT-PCR test were matched to patients with a positive first RT-PCR test on age, sex, and initial admission unit (ward or intensive care). We included 80 cases and 80 controls between March 30, and June 22, 2020. Neither mortality at hospital discharge nor hospital stay length differed between the two groups (P = 0.80 and P = 0.54, respectively). By multivariate analysis, two factors were independently associated with a lower risk of a first false-negative test, namely, headache (adjusted OR [aOR], 0.07; 95% confidence interval [95% CI], 0.01-0.49]; P = 0.007) and fatigue/malaise (aOR, 0.16; 95% CI, 0.03-0.81; P = 0.027); two other factors were independently associated with a higher risk of a first false-negative test, namely, platelets > 207·103 mm-3 (aOR, 3.81; 95% CI, 1.10-13.16]; P = 0.034) and C-reactive protein > 79.8 mg·L-1 (aOR, 4.00; 95% CI, 1.21-13.19; P = 0.023). Patients with suspected COVID-19 whose laboratory tests indicating marked inflammation were at higher risk of a first false-negative RT-PCR test. Strategies involving serial RT-PCR testing must be rigorously evaluated.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , COVID-19/virology , SARS-CoV-2/genetics , Adult , Aged , COVID-19/epidemiology , COVID-19 Testing/statistics & numerical data , Case-Control Studies , False Negative Reactions , Female , Humans , Male , Middle Aged , Reproducibility of Results , Reverse Transcriptase Polymerase Chain Reaction/methods , SARS-CoV-2/isolation & purification , Sensitivity and Specificity
11.
Ann Intensive Care ; 11(1): 20, 2021 Jan 29.
Article in English | MEDLINE | ID: covidwho-1054841

ABSTRACT

BACKGROUND: The aim of this study is to determine whether severe COVID-19 patients harbour a higher risk of ICU-acquired pneumonia. METHODS: This retrospective multicentre cohort study comprised all consecutive patients admitted to seven ICUs for severe COVID-19 pneumonia during the first COVID-19 surge in France. Inclusion criteria were laboratory-confirmed SARS-CoV-2 infection and requirement for invasive mechanical ventilation for 48 h or more. Control groups were two historical cohorts of mechanically ventilated patients admitted to the ICU for bacterial or non-SARS-CoV-2 viral pneumonia. The outcome of interest was the development of ICU-acquired pneumonia. The determinants of ICU-acquired pneumonia were investigated in a multivariate competing risk analysis. RESULT: One hundred and seventy-six patients with severe SARS-CoV-2 pneumonia admitted to the ICU between March 1st and 30th June of 2020 were included into the study. Historical control groups comprised 435 patients with bacterial pneumonia and 48 ones with viral pneumonia. ICU-acquired pneumonia occurred in 52% of COVID-19 patients, whereas in 26% and 23% of patients with bacterial or viral pneumonia, respectively (p < 0.001). Times from initiation of mechanical ventilation to ICU-acquired pneumonia were similar across the three groups. In multivariate analysis, the risk of ICU-acquired pneumonia remained independently associated with underlying COVID-19 (SHR = 2.18; 95 CI 1.2-3.98, p = 0.011). CONCLUSION: COVID-19 appears an independent risk factor of ICU-acquired pneumonia in mechanically ventilated patients with pneumonia. Whether this is driven by immunomodulatory properties by the SARS-CoV-2 or this is related to particular processes of care remains to be investigated.

12.
Scand J Trauma Resusc Emerg Med ; 28(1): 119, 2020 Dec 18.
Article in English | MEDLINE | ID: covidwho-992517

ABSTRACT

BACKGROUND: The COVID-19 outbreak requires a permanent adaptation of practices. Cardiopulmonary resuscitation (CPR) is also involved and we evaluated these changes in the management of out-of-hospital cardiac arrest (OHCA). METHODS: OHCA of medical origins identified from the French National Cardiac Arrest Registry between March 1st and April 31st 2020 (COVID-19 period), were analysed. Different resuscitation characteristics were compared with the same period from the previous year (non-COVID-19 period). RESULTS: Overall, 1005 OHCA during the COVID-19 period and 1620 during the non-COVID-19 period were compared. During the COVID-19 period, bystanders and first aid providers initiated CPR less frequently (49.8% versus 54.9%; difference, - 5.1 percentage points [95% CI, - 9.1 to - 1.2]; and 84.3% vs. 88.7%; difference, - 4.4 percentage points [95% CI, - 7.1 to - 1.6]; respectively) as did mobile medical teams (67.3% vs. 75.0%; difference, - 7.7 percentage points [95% CI, - 11.3 to - 4.1]). First aid providers used defibrillators less often (66.0% vs. 74.1%; difference, - 8.2 percentage points [95% CI, - 11.8 to - 4.6]). Return of spontaneous circulation (ROSC) and D30 survival were lower during the COVID-19 period (19.5% vs. 25.3%; difference, - 5.8 percentage points [95% CI, - 9.0 to - 2.5]; and 2.8% vs. 6.4%; difference, - 3.6 percentage points [95% CI, - 5.2 to - 1.9]; respectively). CONCLUSIONS: During the COVID-19 period, we observed a decrease in CPR initiation regardless of whether patients were suspected of SARS-CoV-2 infection or not. In the current atmosphere, it is important to communicate good resuscitation practices to avoid drastic and lasting reductions in survival rates after an OHCA.


Subject(s)
COVID-19/epidemiology , Cardiopulmonary Resuscitation/methods , Emergency Medical Services , Out-of-Hospital Cardiac Arrest/mortality , Registries , Aged , COVID-19/complications , Female , France/epidemiology , Humans , Male , Middle Aged , Out-of-Hospital Cardiac Arrest/etiology , Out-of-Hospital Cardiac Arrest/therapy , SARS-CoV-2 , Survival Rate/trends
13.
Crit Care Explor ; 2(7): e0166, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-977408

ABSTRACT

Risk factors associated with pulmonary embolism in coronavirus disease 2019 acute respiratory distress syndrome patients deserve to be better known. We therefore performed a post hoc analysis from the COronaVirus-Associated DIsease Study (COVADIS) project, a multicenter observational study gathering 21 ICUs from France (n = 12) and Belgium (n = 9). Three-hundred seventy-five consecutive patients with moderate-to-severe acute respiratory distress syndrome and positive coronavirus disease 2019 were included in the study. At day 28, 15% were diagnosed with pulmonary embolism. Known risk factors for pulmonary embolism including cancer, obesity, diabetes, hypertension, and coronary artery disease were not associated with pulmonary embolism. In the multivariate analysis, younger age (< 65 yr) (odds ratio, 2.14; 1.17-4.03), time between onset of symptoms and antiviral administration greater than or equal to 7 days (odds ratio, 2.39; 1.27-4.73), and use of neuromuscular blockers greater than or equal to 7 days (odds ratio, 1.89; 1.05-3.43) were independently associated with pulmonary embolism. These new findings reinforce the need for prospective studies that will determine the predictors of pulmonary embolism among patients with severe coronavirus disease 2019.

15.
Ann Intensive Care ; 10(1): 131, 2020 Oct 06.
Article in English | MEDLINE | ID: covidwho-835881

ABSTRACT

BACKGROUND: Limited data are available regarding antiviral therapy efficacy in most severe patients under mechanical ventilation for Covid-19-related acute respiratory distress syndrome (ARDS). METHODS: Comparison of antiviral strategies (none, hydroxychloroquine (OHQ), lopinavir/ritonavir (L/R), others (combination or remdesivir) in an observational multicentre cohort of patients with moderate-to-severe Covid-19 ARDS. The primary endpoint was the number of day 28 ventilator-free days (VFD). Patients who died before d28 were considered as having 0 VFD. The variable was dichotomized into "patients still ventilated or dead at day 28" versus "patients weaned and alive at day 28". RESULTS: We analyzed 415 patients (85 treated with standard of care (SOC), 57 with L/R, 220 with OHQ, and 53 others). The median number of d28-VFD was 0 (IQR 0-13) and differed between groups (P = 0.03), SOC patients having the highest d28-VFD. After adjustment for age, sex, Charlson Comorbidity Index, PaO2/FiO2 ratio and plateau pressure and accounting for center effect with a generalized linear mixed model, none of the antiviral strategies increased the chance of being alive and weaned from MV at day 28 compared to the SOC strategy (OR 0.48 CI95% (0.18-1.25); OR 0.96 (0.47-2.02) and OR 1.43 (0.53-4.04) for L/R, OHQ and other treatments, respectively). Acute kidney injury during ICU stay was frequent (55%); its incidence was higher in patients receiving lopinavir (66 vs 53%, P = 0.03). After adjustment for age, sex, BMI, chronic hypertension and chronic renal disease, the use of L/R was associated with an increased risk of renal replacement therapy (RRT). (OR 2.52 CI95% 1.16-5.59). CONCLUSION: In this multicentre observational study of moderate-to-severe Covid-19 ARDS patients, we did not observe any benefit among patients treated with OHQ or L/R compared with SOC. The use of L/R treatment was associated with an increased need for RRT. Take home message Neither hydroxychloroquine nor lopinavir/ritonavir as COVID-19 antiviral treatment is associated with higher ventilator-free days at day 28 when compared with standard of care (no antiviral treatment) in ICU patients under invasive mechanical ventilation. Lopinavir/ritonavir is associated with an increased risk of renal replacement therapy requirement. Tweet COVID-19: Insights from ARDS cohort: no signal of efficacy of any antiviral drugs. Lopinavir/ritonavir may be associated with need for RRT.

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