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1.
Eur J Clin Nutr ; 2022 Aug 26.
Article in English | MEDLINE | ID: covidwho-2016683

ABSTRACT

BACKGROUND/OBJECTIVES: The aim of this post-hoc analysis was to evaluate if epicardial adipose tissue (EAT) quantity and quality, as evaluated by computed tomography (CT), have a different role in the risk of mortality and pulmonary embolism in critically ill COVID-19 patients admitted to an intensive care unit (ICU). SUBJECTS/METHODS: CT derived EAT volume and density, as well as anthropometric and blood biomarkers, were evaluated in a sample of 138 subjects, 109 men and 29 women, for whom CT images and information on pulmonary embolism were available from a total of 313 subjects who were consecutively admitted to the ICU for COVID-19 from the REINSURE-ARDS prospective registry. RESULTS: A total of 28 patients (20.3%) died during the first 28 days after ICU admission. 26 subjects out of 138 had pulmonary embolism (18.8%). Age, weight, BMI, IL-6 levels and pulmonary embolism prevalence were significantly higher across EAT volume tertiles. Subjects who died in the first 28 days from ICU admission were older, had higher EAT volume, D-dimer, LDH and IL-6 level. After adjustment for age and gender, participants in tertile 3 of EAT volume had lower survival at 28 days from ICU admission as compared to subjects in the tertile 1, HR 2.95 (95% C.I. 1.02-8.49), but after adjusting for potential confounders the relation was no longer significant. No relation between EAT density and mortality was observed. From a binary logistic regression, subjects in tertile 3 of EAT volume and in tertile 1 of EAT density showed a 4 times and 3.6 times increased risk of pulmonary embolism, respectively. CONCLUSIONS: ICU subjects affected by severe COVID-19 with higher EAT volume and low EAT density should be carefully monitored and managed with a prompt and aggressive approach, to prevent serious and life-threatening consequences and the increase of hospital treatment costs.

2.
Cell Death Differ ; 29(2): 420-438, 2022 02.
Article in English | MEDLINE | ID: covidwho-1406388

ABSTRACT

Inflammatory responses rapidly detect pathogen invasion and mount a regulated reaction. However, dysregulated anti-pathogen immune responses can provoke life-threatening inflammatory pathologies collectively known as cytokine release syndrome (CRS), exemplified by key clinical phenotypes unearthed during the SARS-CoV-2 pandemic. The underlying pathophysiology of CRS remains elusive. We found that FLIP, a protein that controls caspase-8 death pathways, was highly expressed in myeloid cells of COVID-19 lungs. FLIP controlled CRS by fueling a STAT3-dependent inflammatory program. Indeed, constitutive expression of a viral FLIP homolog in myeloid cells triggered a STAT3-linked, progressive, and fatal inflammatory syndrome in mice, characterized by elevated cytokine output, lymphopenia, lung injury, and multiple organ dysfunctions that mimicked human CRS. As STAT3-targeting approaches relieved inflammation, immune disorders, and organ failures in these mice, targeted intervention towards this pathway could suppress the lethal CRS inflammatory state.


Subject(s)
COVID-19/physiopathology , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/metabolism , Inflammation/metabolism , STAT3 Transcription Factor/metabolism , Aged , Aged, 80 and over , Animals , COVID-19/metabolism , Caspase 8/metabolism , Cytokines/immunology , Cytokines/metabolism , Female , Humans , Male , Mice , Mice, Inbred C57BL , Middle Aged , SARS-CoV-2/immunology , STAT3 Transcription Factor/genetics , Signal Transduction
3.
Sci Rep ; 11(1): 17730, 2021 09 06.
Article in English | MEDLINE | ID: covidwho-1397894

ABSTRACT

The efficacy of non-invasive ventilation (NIV) in acute respiratory failure secondary to SARS-CoV-2 infection remains controversial. Current literature mainly examined efficacy, safety and potential predictors of NIV failure provided out of the intensive care unit (ICU). On the contrary, the outcomes of ICU patients, intubated after NIV failure, remain to be explored. The aims of the present study are: (1) investigating in-hospital mortality in coronavirus disease 2019 (COVID-19) ICU patients receiving endotracheal intubation after NIV failure and (2) assessing whether the length of NIV application affects patient survival. This observational multicenter study included all consecutive COVID-19 adult patients, admitted into the twenty-five ICUs of the COVID-19 VENETO ICU network (February-April 2020), who underwent endotracheal intubation after NIV failure. Among the 704 patients admitted to ICU during the study period, 280 (40%) presented the inclusion criteria and were enrolled. The median age was 69 [60-76] years; 219 patients (78%) were male. In-hospital mortality was 43%. Only the length of NIV application before ICU admission (OR 2.03 (95% CI 1.06-4.98), p = 0.03) and age (OR 1.18 (95% CI 1.04-1.33), p < 0.01) were identified as independent risk factors of in-hospital mortality; whilst the length of NIV after ICU admission did not affect patient outcome. In-hospital mortality of ICU patients intubated after NIV failure was 43%. Days on NIV before ICU admission and age were assessed to be potential risk factors of greater in-hospital mortality.


Subject(s)
COVID-19/therapy , Intensive Care Units/statistics & numerical data , Intubation, Intratracheal/methods , Noninvasive Ventilation/methods , Respiratory Insufficiency/therapy , Aged , COVID-19/complications , COVID-19/virology , Female , Hospital Mortality , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Outcome Assessment, Health Care/methods , Outcome Assessment, Health Care/statistics & numerical data , Respiratory Insufficiency/etiology , Risk Factors , SARS-CoV-2/physiology
4.
Lorenzoni, Giulia, Sella, Nicolò, Boscolo, Annalisa, Azzolina, Danila, Bartolotta, Patrizia, Pasin, Laura, Pettenuzzo, Tommaso, De Cassai, Alessandro, Baratto, Fabio, Toffoletto, Fabio, De Rosa, Silvia, Fullin, Giorgio, Peta, Mario, Rosi, Paolo, Polati, Enrico, Zanella, Alberto, Grasselli, Giacomo, Pesenti, Antonio, Navalesi, Paolo, Gregori, Dario, Tocco, Martina, Pretto, Chiara, Tamburini, Enrico, Fregolent, Davide, Pirelli, Pier Francesco, Marchesin, Davide, Perona, Matteo, Franchetti, Nicola, Paolera, Michele Della, Simoni, Caterina, Falcioni, Tatiana, Tresin, Alessandra, Schiavolin, Chiara, Schiavi, Aldo, Vathi, Sonila, Sartori, Daria, Sorgato, Alice, Pistollato, Elisa, Linassi, Federico, Gianoli, Sara, Gaspari, Silvia, Gruppo, Francesco, Maggiolo, Alessandra, Giurisato, Elena, Furlani, Elisa, Calore, Alvise, Serra, Eugenio, Pittarello, Demetrio, Tiberio, Ivo, Bond, Ottavia, Michieletto, Elisa, Muraro, Luisa, Peralta, Arianna, Persona, Paolo, Petranzan, Enrico, Zarantonello, Francesco, Graziano, Alessandro, Piasentini, Eleonora, Bernardi, Lorenzo, Pianon, Roberto, Mazzon, Davide, Poole, Daniele, Badii, Flavio, Bosco, Enrico, Agostini, Moreno, Trevisiol, Paride, Farnia, Antonio, Altafini, Lorella, Calò, Mauro Antonio, Meggiolaro, Marco, Lazzari, Francesco, Martinello, Ivan, Papaccio, Francesco, di Gregorio, Guido, Bonato, Alfeo, Sgarabotto, Camilla, Montacciani, Francesco, Alessandra, Parnigotto, Gagliardi, Giuseppe, Ferraro, Gioconda, Ongaro, Luigi, Baiocchi, Marco, Danzi, Vinicio, Zanatta, Paolo, Donadello, Katia, Gottin, Leonardo, Sinigaglia, Ezio, da Ros, Alessandra, Marchiotto, Simonetta, Bassanini, Silvia, Zamperini, Massimo, Daroui, Ivan, Mosaner, Walter.
Journal of Anesthesia, Analgesia and Critical Care ; 1(1):3-3, 2021.
Article in English | BioMed Central | ID: covidwho-1388853
5.
Crit Care ; 25(1): 263, 2021 07 28.
Article in English | MEDLINE | ID: covidwho-1331949

ABSTRACT

BACKGROUND: Pathophysiological features of coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) were indicated to be somewhat different from those described in nonCOVID-19 ARDS, because of relatively preserved compliance of the respiratory system despite marked hypoxemia. We aim ascertaining whether respiratory system static compliance (Crs), driving pressure (DP), and tidal volume normalized for ideal body weight (VT/kg IBW) at the 1st day of controlled mechanical ventilation are associated with intensive care unit (ICU) mortality in COVID-19 ARDS. METHODS: Observational multicenter cohort study. All consecutive COVID-19 adult patients admitted to 25 ICUs belonging to the COVID-19 VENETO ICU network (February 28th-April 28th, 2020), who received controlled mechanical ventilation, were screened. Only patients fulfilling ARDS criteria and with complete records of Crs, DP and VT/kg IBW within the 1st day of controlled mechanical ventilation were included. Crs, DP and VT/kg IBW were collected in sedated, paralyzed and supine patients. RESULTS: A total of 704 COVID-19 patients were screened and 241 enrolled. Seventy-one patients (29%) died in ICU. The logistic regression analysis showed that: (1) Crs was not linearly associated with ICU mortality (p value for nonlinearity = 0.01), with a greater risk of death for values < 48 ml/cmH2O; (2) the association between DP and ICU mortality was linear (p value for nonlinearity = 0.68), and increasing DP from 10 to 14 cmH2O caused significant higher odds of in-ICU death (OR 1.45, 95% CI 1.06-1.99); (3) VT/kg IBW was not associated with a significant increase of the risk of death (OR 0.92, 95% CI 0.55-1.52). Multivariable analysis confirmed these findings. CONCLUSIONS: Crs < 48 ml/cmH2O was associated with ICU mortality, while DP was linearly associated with mortality. DP should be kept as low as possible, even in the case of relatively preserved Crs, irrespective of VT/kg IBW, to reduce the risk of death.


Subject(s)
COVID-19/mortality , Respiration, Artificial , Respiratory Distress Syndrome/mortality , Aged , Female , Humans , Intensive Care Units , Intubation , Italy , Male , Middle Aged , Respiratory Distress Syndrome/virology , Tidal Volume
6.
Front Physiol ; 12: 651167, 2021.
Article in English | MEDLINE | ID: covidwho-1241192

ABSTRACT

BACKGROUND: Muscular fatigue and injury are frequently observed in critically ill COVID-19 patients. The aim of this study was to determine whether different muscle adipose tissue depots are associated with mortality and muscle damage in patients affected by COVID-19 admitted to the ICU. METHODS: CT images were obtained in 153 ICU patients with COVID-19 (121 males and 32 females). Height, weight, body mass index (BMI), C-reactive protein, Creatine PhosphoKinase (CPK), muscle density, and intermuscular adipose tissue (IMAT) were measured. RESULTS: Participants in the highest tertile of IMAT/muscle had the shorter 28-day survival from ICU admission as compared to subjects in the first tertile. Estimates derived from the Cox proportional hazard models, after adjustment for age, sex, and BMI, confirmed the results of the survival analysis (HR 3.94, 95% CI: 1.03-15.09). Participants in the lowest tertile of muscle density had the shorter survival at 28 days from ICU admission as compared to subjects in the highest tertile (HR 3.27, 95% CI: 1.18-4.61), but the relationship was no longer significant when age was included in the model. Subjects in the second muscle density tertile did not show an increased risk.Participants in the highest tertile of IMAT/muscle and those in the lowest tertile of muscle density showed both significantly higher CPK adjusted for weight values as evaluated during the first 8 days of hospitalization. CONCLUSION: Our data seem to suggest that higher levels of IMAT/muscle and low muscle density are both associated with higher risk of ICU mortality and muscle injury as evaluated with CPK level.

7.
Nat Commun ; 12(1): 1428, 2021 03 05.
Article in English | MEDLINE | ID: covidwho-1118806

ABSTRACT

Since the beginning of the SARS-CoV-2 pandemic, COVID-19 appeared as a unique disease with unconventional tissue and systemic immune features. Here we show a COVID-19 immune signature associated with severity by integrating single-cell RNA-seq analysis from blood samples and broncho-alveolar lavage fluids with clinical, immunological and functional ex vivo data. This signature is characterized by lung accumulation of naïve lymphoid cells associated with a systemic expansion and activation of myeloid cells. Myeloid-driven immune suppression is a hallmark of COVID-19 evolution, highlighting arginase-1 expression with immune regulatory features of monocytes. Monocyte-dependent and neutrophil-dependent immune suppression loss is associated with fatal clinical outcome in severe patients. Additionally, our analysis shows a lung CXCR6+ effector memory T cell subset is associated with better prognosis in patients with severe COVID-19. In summary, COVID-19-induced myeloid dysregulation and lymphoid impairment establish a condition of 'immune silence' in patients with critical COVID-19.


Subject(s)
COVID-19/immunology , SARS-CoV-2/immunology , Aged , Aged, 80 and over , CD8-Positive T-Lymphocytes/immunology , COVID-19/blood , Case-Control Studies , Cytokines/immunology , Female , Humans , Male , Middle Aged , Monocytes/immunology , Myeloid Cells/immunology , Neutrophils/immunology , T-Lymphocytes/immunology
8.
Nutr Metab Cardiovasc Dis ; 31(3): 762-768, 2021 03 10.
Article in English | MEDLINE | ID: covidwho-1065504

ABSTRACT

BACKGROUND AND AIMS: Recent studies show that obesity is a risk factor for hospital admission and for critical care need in patients with coronavirus disease 2019 (COVID-19). The aim was to determine whether obesity is a risk factor for unfavourable health outcomes in patients affected by COVID-19 admitted to ICU. METHODS AND RESULTS: 95 consecutive patients with COVID-19 (78 males and 18 females) were admitted to ICU and included in the study. Height, weight, BMI, Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, CRP, CPK, ICU and hospital length of stay and comorbidities were evaluated. Participants with obesity had a lower 28 day survival rate from ICU admission than normal weight subjects. Cox proportional hazard model-derived estimates, adjusted for age, gender and comorbidity, confirmed the results of the survival analysis (HR:5.30,95%C.I.1.26-22.34). Obese subjects showed longer hospital and ICU stay as compared with normal weight counterpart.Subjects with obesity showed significantly higher CRP and CPK levels than normal weight subjects. CONCLUSION: In individuals with obesity, careful management and prompt intervention in case of suspected SARS-CoV-2 infection is necessary to prevent the progression of the disease towards severe outcomes and the increase of hospital treatment costs.


Subject(s)
COVID-19/epidemiology , COVID-19/mortality , Obesity/epidemiology , APACHE , Adult , Aged , Aged, 80 and over , Body Mass Index , Critical Illness , Female , Hospitalization/statistics & numerical data , Humans , Intensive Care Units , Length of Stay/statistics & numerical data , Male , Middle Aged , Obesity/mortality , Proportional Hazards Models , Risk Factors , SARS-CoV-2 , Severity of Illness Index
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