• C-reactive protein
• COVID-19 pneumonia
• N-acetylcysteine
• adult
• intensive care unit
• respiratory failure

• Humans
• Acetylcysteine/administration & dosage
• Acetylcysteine/therapeutic use
• Male
• Female
• Respiration, Artificial
• Retrospective Studies
• Middle Aged
• Propensity Score
• Aged
• COVID-19/mortality
• COVID-19/therapy
• COVID-19/complications
• COVID-19 Drug Treatment
• Intensive Care Units
• SARS-CoV-2
• Treatment Outcome
• Administration, Intravenous

• ARDS
• COVID-19
• CRP
• Hyperinflammation
• IL-6
• Tocilizumab

• Humans
• Antibodies, Monoclonal, Humanized/therapeutic use
• Male
• Female
• Retrospective Studies
• Middle Aged
• Aged
• COVID-19 Drug Treatment
• C-Reactive Protein/analysis
• C-Reactive Protein/metabolism
• COVID-19/mortality
• COVID-19/blood
• Interleukin-6/blood
• Biomarkers/blood
• Procalcitonin/blood
• SARS-CoV-2
• Treatment Outcome
• Inflammation
• Aged, 80 and over
• Adult

• Universitätsklinikum Düsseldorf. Anstalt öffentlichen Rechts (8911)

• COVID-19
• IL-6 inhibitors
• IL6
• acute respiratory distress syndrome
• immunomodulators.
• interleukins

• Humans
• Interleukin-6/antagonists & inhibitors
• Interleukin-6/metabolism
• COVID-19 Drug Treatment
• COVID-19/complications
• COVID-19/immunology
• SARS-CoV-2
• Cytokine Release Syndrome/drug therapy
• Respiratory Distress Syndrome/drug therapy
• Respiratory Distress Syndrome/etiology
• Multiple Organ Failure/etiology
• Multiple Organ Failure/drug therapy

• GRANT5585 Deputyship for Research and Innovation at King Faisal University, Al Hofuf, Saudi Arabia

In this study we aimed to evaluate the ability of IMPROVE and IMPROVE-DD scores in predicting in-hospital mortality in patients with severe COVID-19. This prospective observational study included adult patients with severe COVID-19 within 12 h from admission. We recorded patients' demographic and laboratory data, Charlson comorbidity index (CCI), SpO₂ at room air, acute physiology and chronic health evaluation II (APACHE II), IMPROVE score and IMPROVE-DD score. In-hospital mortality and incidence of clinical worsening (the need for invasive mechanical ventilation, vasopressors, renal replacement therapy) were recorded. Our outcomes included the ability of the IMPROVE and IMPROVE-DD to predict in-hospital mortality and clinical worsening using the area under receiver operating characteristic curve (AUC) analysis. Multivariate analysis was used to detect independent risk factors for the study outcomes. Eighty-nine patients were available for the final analysis. The IMPROVE and IMPROVE-DD score showed the highest ability for predicting in-hospital mortality (AUC [95% confidence intervals {CI}] 0.96 [0.90–0.99] and 0.96 [0.90–0.99], respectively) in comparison to other risk stratification tools (APACHE II, CCI, SpO₂). The AUC (95% CI) for IMPROVE and IMPROVE-DD to predict clinical worsening were 0.80 (0.70–0.88) and 0.79 (0.69–0.87), respectively. Using multivariate analysis, IMPROVE-DD and SpO₂ were the only predictors for in-hospital mortality and clinical worsening. In patients with severe COVID-19, high IMPROVE and IMOROVE-DD scores showed excellent ability to predict in-hospital mortality and clinical worsening. Independent risk factors for in-hospital mortality and clinical worsening were IMPROVE-DD and SpO₂.

Severe cases of Coronavirus Disease 2019 (COVID-19) that require admission to the Intensive Care Unit (ICU) and mechanical ventilation assistance show a high mortality rate with currently few therapeutic options available. Severe COVID-19 is characterized by a systemic inflammatory condition, also called “cytokine storm”, which can lead to various multi-organ complications and ultimately death. Lidocaine, a safe local anesthetic that given intravenously is used to treat arrhythmias, has long been reported to have an anti-inflammatory and pro-homeostatic activity.

We studied the capacity of lidocaine to modulate cytokine secretion of mouse and human myeloid cell lines activated by different cytokines or Toll Like Receptor (TLR) ligands (flagellin (FliC), Lipopolysaccharide (LPS), Polyinosinic:polycytidylic acid (Poly I:C) and N-Palmitoyl-S- [2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-(S)-seryl-(S)-lysyl-(S)-lysyl-(S)-lysyl-(S)-lysine x 3HCl (Pam3Cys-SKKKK)) or by Severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2) infection to epithelial cells. Reporter cell lines were used to study modulation of lidocaine of specific signaling pathways.

Lidocaine used in combination with dexamethasone, had an additive effect in the modulation of cellular inflammatory response triggered by Tumoral Necrosis Factor alpha (TNFα), Interleukin 1 beta (IL-1β) as well as different TLR ligands. We also found that lidocaine in combination with dexamethasone modulates the Nuclear factor kappa B (NF-κB) pathway, inflammasome activation as well as interferon gamma receptor (IFNγR) signaling without affecting the type I interferons (Type I IFNs) pathway. Furthermore, we showed that lidocaine and dexamethasone treatment of epithelial cells infected with SARS-CoV-2 modulated the expression of chemokines that contribute to pro-inflammatory effects in severe COVID.

We reported for the first time in vitro anti-inflammatory capacity of lidocaine on SARS-CoV-2 triggered immune pathways. These results indicated the potential of lidocaine to treat COVID-19 patients and add tools to the therapeutic options available for these concerning cases.

• Anti-interleukin-6
• COVID-19
• Inflammation
• Interleukin-6
• Interleukin-6 receptor
• SARS-CoV-2

• acute respiratory failure
• baricitinib
• covid-19
• cpfe
• tocilizumab

We aimed to evaluate the ability of diaphragmatic excursion at hospital admission to predict outcomes in patients with coronavirus disease-2019 (COVID-19).

In this prospective observational study, we included adult patients with severe COVID-19 admitted to a tertiary hospital. Ultrasound examination of the diaphragm was performed within 12 h of admission. Other collected data included peripheral oxygen saturation (SpO₂), respiratory rate, and computed tomography (CT) score. The outcomes included the ability of diaphragmatic excursion, respiratory rate, SpO₂, and CT score at admission to predict the need for ventilatory support (need for non-invasive or invasive ventilation) and patient mortality using the area under the receiver operating characteristic curve (AUC) analysis. Univariate and multivariable analyses about the need for ventilatory support and mortality were performed.

Diaphragmatic excursion showed an excellent ability to predict the need for ventilatory support, which was the highest among respiratory rate, SpO₂, and CT score; the AUCs (95% confidence interval [CI]) was 0.96 (0.85–1.00) for the right diaphragmatic excursion and 0.94 (0.82–0.99) for the left diaphragmatic excursion. The right diaphragmatic excursion also had the highest AUC for predicting mortality in relation to respiratory rate, SpO₂, and CT score. Multivariable analysis revealed that low diaphragmatic excursion was an independent predictor of mortality with an odds ratio (95% CI) of 0.55 (0.31–0.98).

Diaphragmatic excursion on hospital admission can accurately predict the need for ventilatory support and mortality in patients with severe COVID-19. Low diaphragmatic excursion was an independent risk factor for in-hospital mortality.

• COVID-19
• Diaphragmatic dysfunction
• Diaphragmatic excursion
• Mortality
• Ultrasound
• Ventilatory support