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 > 207·10
mm
(aOR, 3.81; 95% CI, 1.10-13.16; P = 0.034) and C-reactive protein > 79.8 mg·L
(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.
Despite evidence suggesting a higher risk of barotrauma during COVID-19-related acute respiratory distress syndrome (ARDS) compared to ARDS due to other causes, data are limited about possible ...associations with patient characteristics, ventilation strategy, and survival.
This prospective observational multicenter study included consecutive patients with moderate-to-severe COVID-19 ARDS requiring invasive mechanical ventilation and managed at any of 12 centers in France and Belgium between March and December 2020. The primary objective was to determine whether barotrauma was associated with ICU mortality (censored on day 90), and the secondary objective was to identify factors associated with barotrauma.
Of 586 patients, 48 (8.2%) experienced barotrauma, including 35 with pneumothorax, 23 with pneumomediastinum, 1 with pneumoperitoneum, and 6 with subcutaneous emphysema. Median time from mechanical ventilation initiation to barotrauma detection was 3 0-17 days. All patients received protective ventilation and nearly half (23/48) were in volume-controlled mode. Barotrauma was associated with higher hospital mortality (P < 0.001) even after adjustment on age, sex, comorbidities, PaO
/FiO
at intubation, plateau pressure at intubation, and center (P < 0.05). The group with barotrauma had a lower mean body mass index (28.6 ± 5.8 vs. 30.3 ± 5.9, P = 0.03) and a higher proportion of patients given corticosteroids (87.5% vs. 63.4%, P = 0.001).
Barotrauma during mechanical ventilation for COVID-19 ARDS was associated with higher hospital mortality.
The coronavirus disease 2019 (COVID-19) pandemic has put significant pressure on hospitals and in particular on intensive care units (ICU). Some patients develop acute hypoxemic respiratory failure ...with profound hypoxia, which likely requires invasive mechanical ventilation during prolonged periods. Corticosteroids have become a cornerstone therapy for patients with severe COVID-19, though only little data are available regarding their potential harms and benefits, especially concerning the risk of a ventilator-associated lower respiratory tract infection (VA-LRTI).
This retrospective multicenter study included patients admitted in four ICUs from Belgium and France for severe COVID-19, who required invasive mechanical ventilation (MV). We compared clinical and demographic variables between patients that received corticosteroids or not, using univariate, multivariate, and Fine and Gray analyses to identify factors influencing VA-LRTI occurrence.
From March 2020 to January 2021, 341 patients required MV for acute respiratory failure related to COVID-19, 322 of whom were included in the analysis, with 60.6% of them receiving corticosteroids. The proportion of VA-LRTI was significantly higher in the early corticosteroid group (63.1% vs. 48.8%,
= 0.011). Multivariable Fine and Gray modeling considering death and extubation as competing events revealed that the factors independently associated with VA-LRTI occurrence were male gender (adjusted sHR:1.7,
= 0.0022) and corticosteroids (adjusted sHR: 1.44,
= 0.022).
in our multicenter retrospective cohort of COVID-19 patients undergoing MV, early corticosteroid therapy was independently associated with VA-LRTI.
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.
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.
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.
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.
Low molecular weight heparins (LMWH) are recommended for thromboprophylaxis in ICU patients but often fail to reach adequate peak anti-Xa activity.
To compare the pharmacokinetic profiles of ...intravenous (IV) versus subcutaneous (SC) route of administration of LMWH.
This was a prospective, monocentric, randomized trial. Patients were randomized to the IV route of administration with a 4-h infusion of nadroparin 3800 IU or to the SC route of administration. Randomization was stratified according to the need for vasopressor or not. Anti-Xa activity was measured at baseline, and at 1, 2, 4, 6, 8, 12 and 24 h after the administration was started.
Sixty patients were included, of whom 30 were randomized to the IV group and 30 to the SC route. Pharmacokinetic profiles were significantly different. Mean peak anti-Xa activity was 0.38 IU/ml in the IV group vs 0.20 IU/ml in the SC group (p < 0.001). Trough values and AUC (0-24 h) were similar in both groups. Pharmacokinetic profiles were similar whether patients received vasopressors or not.
The IV route of administration with a 4-h infusion lead to a significantly higher peak anti-Xa activity without affecting trough value or the AUC (0-24 h). Whether the IV administration of LMWH might improve the efficacy of thromboprophylaxis requires further research.
Registration: ClinicalTrials.gov, NCT04982055, retrospectively registered 08 July 2021, https://clinicaltrials.gov/ct2/show/NCT04982055?cond=NCT04982055&draw=2&rank=1
•The 4-h IV administration of nadroparin lead to a higher peak anti-Xa activity than the SC administration.•Peak anti-Xa activity is not correlated with vasopressor use.•Body mass index is associated with lower peak anti-Xa activities.
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.
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.
The mean Crs in 372 patients was 37.6 ± 13 mL/cmH
O, similar to as in ARDS of other causes. Multivariate linear regression identified chronic hypertension, low PaO
/FiO
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/cmH
O vs 37.8 ± 11.4 mL/cmH
O, p < 0.001). The decrease in Crs was not associated with day-28 outcome.
In a large multicenter cohort of moderate to severe COVID-19 ARDS, mean Crs was decreased below 40 mL/cmH
O 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.
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