Severe 2019 novel coronavirus infectious disease (COVID-19) with pneumonia is associated with high rates of admission to the intensive care unit (ICU). Bacterial coinfection has been reported to be ...rare. We aimed at describing the rate of bacterial coinfection in critically ill adult patients with severe COVID-19 pneumonia. All the patients with laboratory-confirmed severe COVID-19 pneumonia admitted to the ICU of Tenon University-teaching hospital, from February 22 to May 7th, 2020 were included. Respiratory tract specimens were obtained within the first 48 h of ICU admission. During the study period, 101 patients were referred to the ICU for COVID-19 with severe pneumonia. Most patients (
n
= 83; 82.2%) were intubated and mechanically ventilated on ICU admission. Overall, 20 (19.8%) respiratory tract specimens obtained within the first 48 h.
Staphylococcus aureus
was the main pathogen identified, accounting for almost half of the early-onset bacterial etiologies. We found a high prevalence of early-onset bacterial coinfection during severe COVID-19 pneumonia, with a high proportion of S. aureus. Our data support the current WHO guidelines for the management of severe COVID-19 patients, in whom antibiotic therapy directed to respiratory pathogens is recommended.
Purpose
Coronavirus disease 2019 (COVID-19) is creating an unprecedented healthcare crisis. Understanding the determinants of mortality is crucial to optimise intensive care unit (ICU) resource use ...and to identify targets for improving survival.
Methods
In a multicentre retrospective study, we included 379 COVID-19 patients admitted to four ICUs between 20 February and 24 April 2020 and categorised according to time from disease onset to ICU admission. A Cox proportional-hazards model identified factors associated with 28-day mortality.
Results
Median age was 66 years (53–68) and 292 (77%) were men. The main comorbidities included obesity and overweight (67%), hypertension (49.6%) and diabetes (30.1%). Median time from disease onset (i.e., viral symptoms) to ICU admission was 8 (6–11) days (missing for three); 161 (42.5%) patients were admitted within a week of disease onset, 173 (45.6%) between 8 and 14 days, and 42 (11.1%) > 14 days after disease onset; day 28 mortality was 26.4% (22–31) and decreased as time from disease onset to ICU admission increased, from 37 to 21% and 12%, respectively. Patients admitted within the first week had higher SOFA scores, more often had thrombocytopenia or acute kidney injury, had more limited radiographic involvement, and had significantly higher blood IL-6 levels. Age, COPD, immunocompromised status, time from disease onset, troponin concentration, and acute kidney injury were independently associated with mortality.
Conclusion
The excess mortality in patients admitted within a week of disease onset reflected greater non-respiratory severity. Therapeutic interventions against SARS-CoV-2 might impact different clinical endpoints according to time since disease onset.
Background
Growing evidence associates organ dysfunction(s) with impaired metabolism in sepsis. Recent research has increased our understanding of the role of substrate utilization and mitochondrial ...dysfunction in the pathophysiology of sepsis-related organ dysfunction. The purpose of this review is to present this evidence as a coherent whole and to highlight future research directions.
Main text
Sepsis is characterized by systemic and organ-specific changes in metabolism. Alterations of oxygen consumption, increased levels of circulating substrates, impaired glucose and lipid oxidation, and mitochondrial dysfunction are all associated with organ dysfunction and poor outcomes in both animal models and patients. The pathophysiological relevance of bioenergetics and metabolism in the specific examples of sepsis-related immunodeficiency, cerebral dysfunction, cardiomyopathy, acute kidney injury and diaphragmatic failure is also described.
Conclusions
Recent understandings in substrate utilization and mitochondrial dysfunction may pave the way for new diagnostic and therapeutic approaches. These findings could help physicians to identify distinct subgroups of sepsis and to develop personalized treatment strategies. Implications for their use as bioenergetic targets to identify metabolism- and mitochondria-targeted treatments need to be evaluated in future studies.
Background
SARS coronavirus 2 (SARS-CoV-2) is responsible for high morbidity and mortality worldwide, mostly due to the exacerbated inflammatory response observed in critically ill patients. However, ...little is known about the kinetics of the systemic immune response and its association with survival in SARS-CoV-2+ patients admitted in ICU. We aimed to compare the immuno-inflammatory features according to organ failure severity and in-ICU mortality.
Methods
Six-week multicentre study (
N
= 3) including SARS-CoV-2+ patients admitted in ICU. Analysis of plasma biomarkers at days 0 and 3–4 according to organ failure worsening (increase in SOFA score) and 60-day mortality.
Results
101 patients were included. Patients had severe respiratory diseases with PaO2/FiO2 of 155 111–251 mmHg), SAPS II of 37 31–45 and SOFA score of 4 3–7. Eighty-three patients (83%) required endotracheal intubation/mechanical ventilation and among them, 64% were treated with prone position. IL-1β was barely detectable. Baseline IL-6 levels positively correlated with organ failure severity. Baseline IL-6 and CRP levels were significantly higher in patients in the worsening group than in the non-worsening group (278 70–622 vs. 71 29–153 pg/mL,
P
< 0.01; and 178 100–295 vs. 100 37–213 mg/L,
P
< 0.05, respectively). Baseline IL-6 and CRP levels were significantly higher in non-survivors compared to survivors but fibrinogen levels and lymphocyte counts were not different between groups. After adjustment on SOFA score and time from symptom onset to first dosage, IL-6 and CRP remained significantly associated with mortality. IL-6 changes between Day 0 and Day 3–4 were not different according to the outcome.
A contrario
, kinetics of CRP and lymphocyte count were different between survivors and non-survivors.
Conclusions
In SARS-CoV-2+ patients admitted in ICU, a systemic pro-inflammatory signature was associated with clinical worsening and 60-day mortality.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced acute respiratory distress syndrome (ARDS) causes high mortality. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have ...potentially relevant immune-modulatory properties, whose place in ARDS treatment is not established. This phase 2b trial was undertaken to assess the efficacy of UC-MSCs in patients with SARS-CoV-2-induced ARDS.
This multicentre, double-blind, randomized, placebo-controlled trial (STROMA-CoV-2) recruited adults (≥ 18 years) with SARS-CoV-2-induced early (< 96 h) mild-to-severe ARDS in 10 French centres. Patients were randomly assigned to receive three intravenous infusions of 10
UC-MSCs/kg or placebo (0.9% NaCl) over 5 days after recruitment. For the modified intention-to-treat population, the primary endpoint was the partial pressure of oxygen to fractional inspired oxygen (PaO
/FiO
)-ratio change between baseline (day (D) 0) and D7.
Among the 107 patients screened for eligibility from April 6, 2020, to October 29, 2020, 45 were enrolled, randomized and analyzed. PaO
/FiO
changes between D0 and D7 did not differ significantly between the UC-MSCs and placebo groups (medians IQR 54.3 - 15.5 to 93.3 vs 25.3 - 33.3 to 104.6, respectively; ANCOVA estimated treatment effect 7.4, 95% CI - 44.7 to 59.7; P = 0.77). Six (28.6%) of the 21 UC-MSCs recipients and six of 24 (25%) placebo-group patients experienced serious adverse events, none of which were related to UC-MSCs treatment.
D0-to-D7 PaO
/FiO
changes for intravenous UC-MSCs-versus placebo-treated adults with SARS-CoV-2-induced ARDS did not differ significantly. Repeated UC-MSCs infusions were not associated with any serious adverse events during treatment or thereafter (until D28). Larger trials enrolling patients earlier during the course of their ARDS are needed to further assess UC-MSCs efficacy in this context.
NCT04333368. Registered 01 April 2020, https://clinicaltrials.gov/ct2/history/NCT04333368 .
Acute chest syndrome (ACS) is the most serious complication of sickle cell disease. The pathophysiology of ACS may involve lower respiratory tract infection (LRTI), alveolar hypoventilation and ...atelectasis, bone infarcts-driven fat embolism, and in situ pulmonary artery thrombosis. One of the most challenging issues for the physicians is to diagnose LRTI as the cause of ACS. The use of a respiratory multiplex PCR (mPCR) for the diagnosis of LRTI has not been assessed in sickle-cell adult patients with ACS. To describe the spectrum of infectious aetiologies of severe ACS, using a diagnostic approach combining conventional tests and mPCR. A non-interventional monocenter prospective study involving all the consecutive sickle-cell adult patients with ACS admitted to the intensive care unit (ICU). Microbiological investigation included conventional tests and a nasopharyngeal swab for mPCR. Altogether, 36 patients were enrolled, of whom 30 (83%) had complete microbiological investigations. A bacterial microorganism, mostly Staphylococcus aureus (n = 8), was identified in 11 patients. There was no pneumonia-associated intracellular bacterial pathogen. A respiratory virus was identified in six patients. Using both conventional tests and nasopharyngeal mPCR, a microbiological documentation was obtained in half of adult ACS patients admitted to the ICU. Pyogenic bacteria, especially S. aureus, predominated.
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to alleviate symptoms during community-acquired pneumonia (CAP), while neither clinical data nor guidelines encourage this use. ...Experimental data suggest that NSAIDs impair neutrophil intrinsic functions, their recruitment to the inflammatory site, and the resolution of inflammatory processes after acute pulmonary bacterial challenge. During CAP, numerous observational data collected in hospitalized children, hospitalized adults, and adults admitted to intensive care units (ICUs) support a strong association between pre-hospital NSAID exposure and a delayed hospital referral, a delayed administration of antibiotic therapy, and the occurrence of pleuropulmonary complications, even in the only study that has accounted for a protopathic bias. Other endpoints have been described including a longer duration of antibiotic therapy and a greater hospital length of stay. In all adult series, patients exposed to NSAIDs were younger and had fewer comorbidities. The mechanisms by which NSAID use would entail a complicated course in pneumonia still remain uncertain. The temporal hypothesis and the immunological hypothesis are the two main emerging hypotheses. Current data strongly support an association between NSAID intake during the outpatient treatment of CAP and a complicated course. This should encourage experts and scientific societies to strongly advise against the use of NSAIDs in the management of lower respiratory tract infections.
Background
While acute kidney injury (AKI) is frequent in severe SARS-CoV2-related pneumonia ICU patients, few data are still available about its risk factors.
Methods
Retrospective observational ...study performed in four university affiliated hospitals in Paris. AKI was defined according to the KIDGO guidelines. Factors associated with AKI were picked up using multivariable mixed-effects logistic regression. Independent risk factors of day 28 mortality were assessed using Cox model.
Results
379 patients (median age 62 53,69, 77% of male) were included. Half of the patients had AKI (
n
= 195, 52%) including 58 patients (15%) with AKI stage 1, 44 patients (12%) with AKI stage 2, and 93 patients (25% with AKI stage 3). Chronic kidney disease (OR 7.41; 95% CI 2.98–18.4), need for invasive mechanical ventilation at day 1 (OR 4.83; 95% CI 2.26–10.3), need for vasopressors at day 1 (OR 2.1; 95% CI 1.05–4.21) were associated with increased risk of AKI. Day 28 mortality in the cohort was 26.4% and was higher in patients with AKI (37.4 vs. 14.7%,
P
< 0.001). Neither AKI (HR 1.35; 95% CI 0.78–2.32) nor AKI stage were associated with mortality (HR 95% CI for stage 1, 2 and 3 when compared to no AKI of, respectively, 1.02 0.49–2.10, 1.73 0.81–3.68 and 1.42 0.78–2.58).
Conclusion
In this large cohort of SARS-CoV2-related pneumonia patients admitted to the ICU, AKI was frequent, mostly driven by preexisting chronic kidney disease and life sustaining therapies, with unclear adjusted relationship with day 28 outcome.
Spontaneous pneumomediastinum (SP) has been described early during the COVID-19 pandemic in large series of patients with severe pneumonia, but most patients were receiving invasive mechanical ...ventilation (IMV) at the time of SP diagnosis. In this retrospective multicenter observational study, we aimed at describing the prevalence and outcomes of SP during severe COVID-19 with pneumonia before any IMV, to rule out mechanisms induced by IMV in the development of pneumomediastinum.Among 549 patients, 21 patients (4%) developed a SP while receiving non-invasive respiratory support, after a median of 6 days 4-12 from ICU admission. The proportion of patients requiring IMV was similar. However, the time to tracheal intubation was longer in patients with SP (6 days 5-13 vs. 2 days 1-4; P = 0.00002), with a higher first-line use of non-invasive ventilation (n = 11; 52% vs. n = 150; 28%; P = 0.02). The 21 patients who developed a SP had persisting signs of severe lung disease and respiratory failure with lower ROX index between ICU admission and occurrence of SP (3.94 3.15-5.55 at admission vs. 3.25 2.73-4.02 the day preceding SP; P = 0.1), which may underline potential indirect signals of Patient-self inflicted lung injury (P-SILI).In this series of critically ill COVID-19 patients, the prevalence of SP without IMV was not uncommon, affecting 4% of patients. They received more often vasopressors and had a longer ICU length of stay, as compared with their counterparts. One pathophysiological mechanism may potentially be carried out by P-SILI related to a prolonged respiratory failure, as underlined by a delayed use of IMV and the evolution of the ROX index between ICU admission and the day preceding SP.
Multiplex polymerase chain reaction (mPCR) enables recovery of viruses from airways of patients with community-acquired pneumonia (CAP), although their clinical impact remains uncertain.
Among ...consecutive adult patients who had undergone a mPCR within 72 hours following their admission to one intensive care unit (ICU), we retrospectively included those with a final diagnosis of CAP. Four etiology groups were clustered: bacterial, viral, mixed (viral-bacterial) and no etiology. A composite criterion of complicated course (hospital death or mechanical ventilation > 7 days) was used. A subgroup analysis compared patients with bacterial and viral-bacterial CAP matched on the bacterial pathogens.
Among 174 patients (132 men 76 %, age 63 53-75 years, SAPSII 38 27;55, median PSI score 106 78;130), bacterial, viral, mixed and no etiology groups gathered 46 (26 %), 53 (31 %), 45 (26 %) and 30 (17 %) patients, respectively. Virus-infected patients displayed a high creatine kinase serum level, a low platelet count, and a trend toward more frequent alveolar-interstitial infiltrates. A complicated course was more frequent in the mixed group (31/45, 69 %), as compared to bacterial (18/46, 39 %), viral (15/53, 28 %) and no etiology (12/30, 40 %) groups (p < 0.01). In multivariate analysis, the mixed (viral-bacterial) infection was independently associated with complicated course (reference: bacterial pneumonia; OR, 3.58; CI 95 %, 1.16-11; p = 0.03). The subgroup analysis of bacteria-matched patients confirmed these findings.
Viral-bacterial coinfection during severe CAP in adults is associated with an impaired presentation and a complicated course.
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