Gut Microbiota Diversity and C-Reactive Protein Are Predictors of Disease Severity in COVID-19 Patients.

The risk factors for coronavirus disease 2019 (COVID-19) severity are still poorly understood. Considering the pivotal role of the gut microbiota on host immune and inflammatory functions, we investigated the association between changes in the gut microbiota composition and the clinical severity of COVID-19. We conducted a multicenter cross-sectional study prospectively enrolling 115 COVID-19 patients categorized according to: (1) the WHO Clinical Progression Scale-mild, 19 (16.5%); moderate, 37 (32.2%); or severe, 59 (51.3%), and (2) the location of recovery from COVID-19-ambulatory, 14 (household isolation, 12.2%); hospitalized in ward, 40 (34.8%); or hospitalized in the intensive care unit, 61 (53.0%). Gut microbiota analysis was performed through 16S rRNA gene sequencing, and the data obtained were further related to the clinical parameters of COVID-19 patients. The risk factors for COVID-19 severity were identified by univariate and multivariable logistic regression models. In comparison to mild COVID-19 patients, the gut microbiota of moderate and severe patients have: (a) lower Firmicutes/Bacteroidetes ratio; (b) higher abundance of Proteobacteria; and (c) lower abundance of beneficial butyrate-producing bacteria such as the genera Roseburia and Lachnospira. Multivariable regression analysis showed that the Shannon diversity index [odds ratio (OR) = 2.85, 95% CI = 1.09-7.41, p = 0.032) and C-reactive protein (OR = 3.45, 95% CI = 1.33-8.91, p = 0.011) are risk factors for severe COVID-19 (a score of 6 or higher in the WHO Clinical Progression Scale). In conclusion, our results demonstrated that hospitalized patients with moderate and severe COVID-19 have microbial signatures of gut dysbiosis; for the first time, the gut microbiota diversity is pointed out as a prognostic biomarker of COVID-19 severity.

An integrated program of extracorporeal membrane oxygenation (ECMO) assisted cardiopulmonary resuscitation and uncontrolled donation after circulatory determination of death in refractory cardiac arrest.

AIM: To assess the feasibility of an integrated program of extracorporeal cardiopulmonary resuscitation (ECPR) and uncontrolled donation after circulatory determination of death (uDCDD) in refractory cardiac arrest (rCA). METHODS: Single center, prospective, observational study of selected patients with in-hospital (IHCA) and out-of-hospital (OHCA) rCA occurring in an urban area of ∼1.5 million inhabitants, between October-2016 and May-2018. 65 year old or younger patients without significant bleeding or comorbidities with witnessed nonasystolic cardiac arrests were triaged to ECPR if they had a reversible cause and high quality CPR lasting < 60 min. Otherwise they were considered for uDCDD after a ten minute no touch period using normothermic regional perfusion. RESULTS: 58 patients were included, of which 41 (71%) were OHCA and 18 (31%) had ECPR initiated. Median age was 52 (IQR 45-56) years. Cannulation was successful in 49/58 (84%) cases. Compared to ECPR, patients referred for uDCDD were more frequently OHCA (90 vs. 28%), had bystander CPR (28 vs. 83%) and prolonged low-flow period (40 (35-50) vs. 60 (49-78) min). Survival to hospital discharge with full neurological recovery (cerebral performance category 1) occurred in 6/18 (33%) ECPR patients. uDCDD resulted in transplantation of 44 kidneys. CONCLUSIONS: An integrated program for rCA consisting of a formal pathway to uDCDD referral in ECPR ineligible patients is feasible. ECPR-referred patients had a reasonable survival with full neurologic recovery. Successful kidney transplantation was achieved with uDCDD.

Extracorporeal Membrane Oxygenation for Refractory Severe Respiratory Failure in Acute Interstitial Pneumonia.

Acute interstitial pneumonia (AIP) is a rare idiopathic interstitial lung disease with rapid progressive respiratory failure and high mortality. In the present report, three cases of AIP complicated by refractory respiratory failure supported with extracorporeal membrane oxygenation (ECMO) are presented. One male and two female patients (ages 27-59) were included. Venovenous ECMO support was provided using miniaturized systems, with two-site femoro-jugular circuit configuration. Despite lung protective ventilation, prone position and neuromuscular blockade, refractory respiratory failure of unknown etiology supervened (ratio of arterial oxygen partial pressure to fractional inspired oxygen 46-130) and ECMO was initiated after 3-7 days of mechanical ventilation. AIP diagnosis was established after exclusion of infectious and noninfectious acute respiratory distress syndrome on the basis of clinical and analytical data, bronchoalveolar lavage analysis and lung imaging, with a confirmatory surgical lung biopsy revealing diffuse alveolar damage of unknown etiology. Immunosuppressive treatment consisted in high-dose corticosteroids and cyclophosphamide in one case. Two patients survived to hospital discharge. ECMO allowed AIP diagnosis and treatment in the presence of refractory respiratory failure, therefore reducing ventilator-induced lung injury and bridging lung recovery in two patients. ECMO referral should be considered in refractory respiratory failure if AIP is suspected.