Abstract
The objective of the present study was to identify biological signatures of severe coronavirus disease 2019 (COVID-19) predictive of admission in the intensive care unit (ICU). Over 170 ...immunological markers were investigated in a ‘discovery’ cohort (n = 98 patients) of the Lausanne University Hospital (LUH-1). Here we report that 13 out of 49 cytokines were significantly associated with ICU admission in the three cohorts (
P
< 0.05 to
P
< 0.001), while cellular immunological markers lacked power in discriminating between ICU and non-ICU patients. The cytokine results were confirmed in two ‘validation’ cohorts,
i.e
. the French COVID-19 Study (FCS; n = 62) and a second LUH-2 cohort (n = 47). The combination of hepatocyte growth factor (HGF) and C-X-C motif chemokine ligand 13 (CXCL13) was the best predictor of ICU admission (positive and negative predictive values ranging from 81.8% to 93.1% and 85.2% to 94.4% in the 3 cohorts) and occurrence of death during patient follow-up (8.8 fold higher likelihood of death when both cytokines were increased). Of note, HGF is a pleiotropic cytokine with anti-inflammatory properties playing a fundamental role in lung tissue repair, and CXCL13, a pro-inflammatory chemokine associated with pulmonary fibrosis and regulating the maturation of B cell response. Up-regulation of HGF reflects the most powerful counter-regulatory mechanism of the host immune response to antagonize the pro-inflammatory cytokines including CXCL13 and to prevent lung fibrosis in COVID-19 patients.
This study aims to describe the epidemiology of COVID-19 patients in a Swiss university hospital.
This retrospective observational study included all adult patients hospitalized with a laboratory ...confirmed SARS-CoV-2 infection from March 1 to March 25, 2020. We extracted data from electronic health records. The primary outcome was the need to mechanical ventilation at day 14. We used multivariate logistic regression to identify risk factors for mechanical ventilation. Follow-up was of at least 14 days.
145 patients were included in the multivariate model, of whom 36 (24.8%) needed mechanical ventilation at 14 days. The median time from symptoms onset to mechanical ventilation was 9·5 days (IQR 7.00, 12.75). Multivariable regression showed increased odds of mechanical ventilation with age (OR 1.09 per year, 95% CI 1.03-1.16, p = 0.002), in males (OR 6.99, 95% CI 1.68-29.03, p = 0.007), in patients who presented with a qSOFA score ≥2 (OR 7.24, 95% CI 1.64-32.03, p = 0.009), with bilateral infiltrate (OR 18.92, 3.94-98.23, p<0.001) or with a CRP of 40 mg/l or greater (OR 5.44, 1.18-25.25; p = 0.030) on admission. Patients with more than seven days of symptoms on admission had decreased odds of mechanical ventilation (0.087, 95% CI 0.02-0.38, p = 0.001).
This study gives some insight in the epidemiology and clinical course of patients admitted in a European tertiary hospital with SARS-CoV-2 infection. Age, male sex, high qSOFA score, CRP of 40 mg/l or greater and a bilateral radiological infiltrate could help clinicians identify patients at high risk for mechanical ventilation.
Sepsis is a leading cause of morbidity and mortality. Prompt recognition and management are critical to improve outcomes.
We conducted a survey among nurses and physicians of all adult departments of ...the Lausanne University Hospital (LUH) and paramedics transporting patients to our hospital. Measured outcomes included professionals' demographics (age, profession, seniority, unit of activity), quantification of prior sepsis education, self-evaluation, and knowledge of sepsis epidemiology, definition, recognition, and management. Correlation between surveyed personnel and sepsis perceptions and knowledge were assessed with univariable and multivariable logistic regression models.
Between January and October 2020, we contacted 1'216 of the 4'417 professionals (27.5%) of the LUH, of whom 1'116 (91.8%) completed the survey, including 619 of 2'463 (25.1%) nurses, 348 of 1'664 (20.9%) physicians and 149 of 290 (51.4%) paramedics. While 98.5% of the participants were familiar with the word "sepsis" (97.4% of nurses, 100% of physicians and 99.3% of paramedics), only 13% of them (physicians: 28.4%, nurses: 5.9%, paramedics: 6.8%) correctly identified the Sepsis-3 consensus definition. Similarly, only 48% and 49.3% of the physicians and 10.1% an 11.9% of the nurses knew that SOFA was a sepsis defining score and that the qSOFA score was a predictor of increased mortality, respectively. Furthermore, 15.8% of the physicians and 1.0% of the nurses knew the three components of the qSOFA score. For patients with suspected sepsis, 96.1%, 91.6% and 75.8% of physicians respectively chose blood cultures, broad-spectrum antibiotics and fluid resuscitation as therapeutic interventions to be initiated within 1 (76.4%) to 3 (18.2%) hours. For nurses and physicians, recent training correlated with knowledge of SOFA score (ORs 95%CI: 3.956 2.018-7.752 and 2.617 1.527-4.485) and qSOFA (ORs 95%CI: 5.804 2.653-9.742 and 2.291 1.342-3.910) scores purposes. Furthermore, recent training also correlated with adequate sepsis definition (ORs 95%CI: 1.839 1.026-3.295) and the components of qSOFA (ORs 95%CI: 2.388 1.110-5.136) in physicians.
This sepsis survey conducted among physicians, nurses and paramedics of a tertiary Swiss medical center identified a deficit of sepsis awareness and knowledge reflecting a lack of sepsis-specific continuing education requiring immediate corrective measures.
We used unsupervised immunophenotyping of blood leukocytes and measured cytokine production by innate immune cell exposed to LPS and R848. We show that COVID‐19 induces a rapid, transient ...upregulation of myeloid‐derived suppressor cells (MDSCs) accompanied by a rapid, sustained (up to 3 months) hyporesponsiveness of dendritic cells and monocytes. Blood MDSCs may represent biomarkers and targets for intervention strategies in COVID‐19 patients.
Sirtuin 2 (SIRT2) and SIRT3 are cytoplasmic and mitochondrial NAD-dependent deacetylases. SIRT2 and SIRT3 target proteins involved in metabolic, proliferation and inflammation pathways and have been ...implicated in the pathogenesis of neurodegenerative, metabolic and oncologic disorders. Both pro- and anti-inflammatory effects have been attributed to SIRT2 and SIRT3, and single deficiency in SIRT2 or SIRT3 had minor or no impact on antimicrobial innate immune responses. Here, we generated a SIRT2/3 double deficient mouse line to study the interactions between SIRT2 and SIRT3. SIRT2/3
mice developed normally and showed subtle alterations of immune cell populations in the bone marrow, thymus, spleen, blood and peritoneal cavity that contained notably more anti-inflammatory B-1a cells and less NK cells.
, SIRT2/3
macrophages favored fatty acid oxidation (FAO) over glycolysis and produced increased levels of both proinflammatory and anti-inflammatory cytokines. In line with metabolic adaptation and increased numbers of peritoneal B-1a cells, SIRT2/3
mice were robustly protected from endotoxemia. Yet, SIRT2/3 double deficiency did not modify endotoxin tolerance. Overall, these data suggest that sirtuins can act in concert or compensate each other for certain immune functions, a parameter to be considered for drug development. Moreover, inhibitors targeting multiple sirtuins developed for clinical purposes may be useful to treat inflammatory diseases.
Background. Coronavirus disease 2019 (COVID-19) can result in profound changes in blood coagulation. The aim of the study was to determine the incidence and predictors of venous thromboembolic events ...(VTE) among patients with COVID-19 requiring hospital admission. Subjects and Methods. We performed a retrospective study at the Lausanne University Hospital with patients admitted because of COVID-19 from February 28 to April 30, 2020. Results. Among 443 patients with COVID-19, VTE was diagnosed in 41 patients (9.3%; 27 pulmonary embolisms, 12 deep vein thrombosis, one pulmonary embolism and deep vein thrombosis, one portal vein thrombosis). VTE was diagnosed already upon admission in 14 (34.1%) patients and 27 (65.9%) during hospital stay (18 in ICU and nine in wards outside the ICU). Multivariate analysis revealed D-dimer value>3,120 ng/ml (P<0.001; OR 15.8, 95% CI 4.7-52.9) and duration of 8 days or more from COVID-19 symptoms onset to presentation (P 0.020; OR 4.8, 95% CI 1.3-18.3) to be independently associated with VTE upon admission. D-dimer value≥3,000 ng/l combined with a Wells score for PE≥2 was highly specific (sensitivity 57.1%, specificity 91.6%) in detecting VTE upon admission. Development of VTE during hospitalization was independently associated with D-dimer value>5,611 ng/ml (P<0.001; OR 6.3, 95% CI 2.4-16.2) and mechanical ventilation (P<0.001; OR 5.9, 95% CI 2.3-15.1). Conclusions. VTE seems to be a common COVID-19 complication upon admission and during hospitalization, especially in ICU. The combination of Wells≥2 score and D−dimer≥3,000 ng/l is a good predictor of VTE at admission.
ObjectiveTo assess the SARS-CoV-2 transmission in healthcare workers (HCWs) using seroprevalence as a surrogate marker of infection in our tertiary care centre according to ...exposure.DesignSeroprevalence cross-sectional study.SettingSingle centre at the end of the first COVID-19 wave in Lausanne, Switzerland.Participants1874 of 4074 responders randomly selected (46% response rate), stratified by work category among the 13 474 (13.9%) HCWs.Main outcome measuresEvaluation of SARS-CoV-2 serostatus paired with a questionnaire of SARS-CoV-2 acquisition risk factors internal and external to the workplace.ResultsThe overall SARS-CoV-2 seroprevalence rate among HCWs was 10.0% (95% CI 8.7% to 11.5%). HCWs with daily patient contact did not experience increased rates of seropositivity relative to those without (10.3% vs 9.6%, respectively, p=0.64). HCWs with direct contact with patients with COVID-19 or working in COVID-19 units did not experience increased seropositivity rates relative to their counterparts (10.4% vs 9.8%, p=0.69 and 10.6% vs 9.9%, p=0.69, respectively). However, specific locations of contact with patients irrespective of COVID-19 status—in patient rooms or reception areas—did correlate with increased rates of seropositivity (11.9% vs 7.5%, p=0.019 and 14.3% vs 9.2%, p=0.025, respectively). In contrast, HCWs with a suspected or proven SARS-CoV-2-infected household contact had significantly higher seropositivity rates than those without such contacts (19.0% vs 8.7%, p<0.001 and 42.1% vs 9.4%, p<0.001, respectively). Finally, consistent use of a mask on public transportation correlated with decreased seroprevalence (5.3% for mask users vs 11.2% for intermittent or no mask use, p=0.030).ConclusionsThe overall seroprevalence was 10% without significant differences in seroprevalence between HCWs exposed to patients with COVID-19 and HCWs not exposed. This suggests that, once fully in place, protective measures limited SARS-CoV-2 occupational acquisition within the hospital environment. SARS-CoV-2 seroconversion among HCWs was associated primarily with community risk factors, particularly household transmission.
Asymptomatic bacteriuria is frequently encountered in clinical practice and should be treated only in pregnant women and before invasive urological procedures. Inappropriate treatment of asymptomatic ...bacteriuria is associated with numerous adverse effects including allergic reactions, increased antibiotics resistance and increase risk of Clostridioides difficile infection. Positive urinary culture often leads to antimicrobial treatment, irrespective of urinary symptoms. Therefore, urine analysis and culture should be performed only in symptomatic individuals or in asymptomatic individuals with a clear indication for treatment.
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