Echocardiography Before Extracorporeal Membrane Oxygenation in Refractory Respiratory Failure: SARS-CoV-2 Infection Versus Other Etiologies.

OBJECTIVES: The study authors hypothesized that in patients with SARS-CoV-2, COVID-19-related refractory respiratory failure requiring extracorporeal membrane oxygenation (ECMO) support echocardiographic findings (just before ECMO implantation) would be different from those observed in patients with refractory respiratory failure from different etiologies. DESIGN: A single-center observational study. SETTING: At an intensive care unit (ICU). PARTICIPANTS: A total of 61 consecutive patients with refractory COVID-19-related respiratory failure (COVID-19 series) and 74 patients with refractory acute respiratory disease syndrome from other etiologies (no COVID-19 series), all needing ECMO support. INTERVENTIONS: Echocardiogram pre-ECMO. MEASUREMENTS AND MAIN RESULTS: Right ventricle dilatation and dysfunction were defined in the presence of the RV end-diastolic area and/or left ventricle end-diastolic area (LVEDA >0.6 and tricuspid annular plane systolic excursion [TAPSE] <15 mm. Patients in the COVID-19 series showed a higher body mass index (p < 0.001) and a lower Sequential Organ Failure Assessment score (p = 0.002). In-ICU mortality rates were comparable between the 2 subgroups. Echocardiograms performed in all patients before ECMO implantation revealed an incidence of RV dilatation that was higher in patients in the COVID-19 series (p < 0.001), and they also showed higher values of systolic pulmonary artery pressure (sPAP) (p < 0.001) and lower TAPSE and/or sPAP (p < 0.001). The multivariate logistic regression analysis showed that COVID-19-related respiratory failure was not associated with early mortality. The presence of RV dilatation and the uncoupling of RV function and pulmonary circulation were associated independently with COVID-19 respiratory failure. CONCLUSIONS: The presence of RV dilatation and an altered coupling between RVe function and pulmonary vasculature (as indicated by TAPSE and/or sPAP) are associated strictly with COVID-19-related refractory respiratory failure needing ECMO support.

Characteristics of COVID-19 vaccinated and unvaccinated patients admitted to Careggi University Hospital, Florence, Italy.

More than 11.5 billion COVID-19 vaccine doses have been administered around the world. Although vaccine effectiveness for severe infections is reported to be 89.0%, breakthrough infections are common and may lead to severe outcome in fragile population. We conducted a real-world observational study on 420 COVID-19 admitted patients from July 2021 to January 2022 in a tertiary level Italian hospital. We collected patient's vaccination and SARS-CoV-2 serological status, SARS-CoV-2 treatments, oxygen supports, intensive (ICU) and subintensive (sub-ICU) care unit admissions, length of staying (LoS) and in-hospital mortality. One-hundred-seventy-two vaccinated and 248 unvaccinated patients were admitted during the study period. Vaccinated group (Vg) had a significantly more elevated Charlson Comorbidity Index than Unvaccinated group (UVg), and no statistical differences were found in terms of in-hospital mortality, LoS or ICU and sub-ICU admissions. Among Vg, anti-S antibodies were detected in 86.18% of patients (seropositives). Vaccinated seronegative patients' in-hospital mortality was significantly higher than vaccinated seropositive patients (33.33% vs 10.69%, p = 0.0055): in particular, mortality rate in 45-69 years old population was higher in vaccinated seronegative group, and comparable in patients ≥ 70 years old. No differences in terms of outcome were registered between Vg and UVg, taking into account that Vg was considerably older and with more comorbidities. In line with other recent observations, higher mortality rate was evidenced for seronegative vaccinated patients. Primary prophylaxis and early treatments result to be necessary, especially for older and immunosuppressed populations.

Clinical Significance of Right Ventricle Echocardiographic Patterns in Critically-Ill COVID-Related Acute Respiratory Distress Syndrome "On Behalf of Protecting the Right Ventricle Network (PRORVnet)".

We assessed whether right ventricle (RV) alterations and their development may have clinical significance in critically-ill Coronavirus Disease (COVID) patients, as detected by serial echocardiograms during Intensive Care Unit (ICU) course. This observational single center study included 98 consecutive patients with COVID-related acute respiratory distress syndrome (ARDS). Three subgroups were considered: RV Dysfunction (Dys) on admission (10/98, 10%), developed RV Dys (17/98, 17%), and no RV Dys (71/98, 73%). Overall mortality at 3 months was 46.9%. The first subgroup was characterized by the highest need for Extracorporeal Membrane Oxygenation (ECMO) support (P < .001) and a systemic inflammatory activation (as indicated by increased D-dimer), the second one by the lowest PaO2/FiO2 (P/F). At multivariate regression analysis, age and Sequential Organ Failure Assessment score were independent predictors for mortality. Different RV echo patterns were observed in critically ill patients presenting with COVID-related ARDS during ICU stay. RV Dys on admission was characterized by a high inflammatory activation while patients who developed RV Dys during ICU stay showed lowest P/F. Both these two subgroups identify patients with a severe COVID disease which in a high percentage of cases was unresponsive to standard treatment and required the use of ECMO.

Dynamic assessment of surge capacity in a large hospital network during COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has provided an unprecedented scenario to deepen knowledge of surge capacity (SC), assessment of which remains a challenge. This study reports a large-scale experience of a multi-hospital network, with the aim of evaluating the characteristics of different hospitals involved in the response and of measuring a real-time SC based on two complementary modalities (actual, base) referring to the intensive care units (ICU). METHODS: Data analysis referred to two consecutive pandemic waves (March-December 2020). Regarding SC, two different levels of analysis are considered: single hospital category (referring to a six-level categorization based on the number of hospital beds) and multi-hospital wide (referring to the response of the entire hospital network). RESULTS: During the period of 114 days, the analysis revealed a key role of the biggest hospitals (>Category-4) in terms of involvement in the pandemic response. In terms of SC, Category-4 hospitals showed the highest mean SC values, irrespective of the calculation method and level of analysis. At the multi-hospital level, the analysis revealed an overall ICU-SC (base) of 84.4% and an ICU-SC (actual) of 106.5%. CONCLUSIONS: The results provide benchmarks to better understand ICU hospital response capacity, highlighting the need for a more flexible approach to SC definition.

Coupling of right ventricular function to pulmonary circulation as an independent predictor for non invasive ventilation failure in SARSCoV 2-related acute respiratory distress syndrome.

Study objectives: To assess whether echocardiography, systematically performed, could help in risk stratifying patients with acute respiratory distress syndrome (ARDS) due to SARS-CoV2 (COVID) infection for non invasive ventilation (NIV) failure. Design: Observational single center investigation. Setting: Intensive care unit. Interventions: Echocardiography. Outcome measures: NIV failure. Main results: Seventy-five patients were included in our study. In respect to patients who did not need mechanical ventilation (NIV success), those in the NIV failure subgroup (31 patients, 41 %) were older, with more comorbidities and showed a higher SOFA score and LOS. Higher values of NTpro BNP, CRP and D-dimer were observed in the NIV failure subgroup who exhibited a higher ICU mortality rate. At echocardiographic examination, the NIV failure subgroup showed higher values of RV/LV ratio, systolic pulmonary arterial pressure (sPAP) and lower values of tricuspid annular plane systolic excursion (TAPSE)/SPAP, and PaO2/FiO2. At logistic regression analysis TAPSE/sPAP resulted an independent predictor of NIV failure. At receiving operating characteristic curve analysis, the TAPSE/SPAP cut-off of 0.575 mm/mm Hg showed a sensitivity of 97 % and a specificity of 48 %. Conclusions: Our results documented a marked uncoupling of right ventricular function from the pulmonary circulation (as indicated by TAPSE/sPAP) in COVID-related ARDS treated with non invasive ventilation and the measurement of this parameter, performed on ICU admission, provides independent prognostic relevance for NIV failure.

Perinatal outcomes of pregnant women with severe COVID-19 requiring extracorporeal membrane oxygenation (ECMO): a case series and literature review.

PURPOSE: Pregnant women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have a higher risk of hospitalization, admission to intensive care unit (ICU) and invasive ventilation, and of acute respiratory distress syndrome (ARDS). In case of ARDS and critical severe coronavirus disease 2019 (COVID-19), the use of extracorporeal membrane oxygenation (ECMO) is recommended when other respiratory support strategies (oxygen insufflation, non-invasive ventilation [NIV], invasive ventilation through an endotracheal tube) are insufficient. However, available data on ECMO in pregnant and postpartum women with critical COVID-19 are very limited. METHODS: A case series of three critically ill pregnant women who required ECMO support for COVID-19 in pregnancy and/or in the postpartum period. RESULTS: The first patient tested positive for COVID-19 during the second trimester, she developed ARDS and required ECMO for 38 days. She was discharged in good general conditions and a cesarean-section [CS] at term was performed for obstetric indication. The second patient developed COVID-19-related ARDS at 28 weeks of gestation. During ECMO, she experienced a precipitous vaginal delivery at 31 weeks and 6 days of gestation. She was discharged 1 month later in good general conditions. The third patient, an obese 43-year-old woman, tested positive at 38 weeks and 2 days of gestation. Because of the worsening of clinical condition, a CS was performed, and she underwent ECMO. 143 days after the CS, she died because of sepsis and multiple organ failure (MOF). Thrombosis, hemorrhage and infections were the main complications among our patients. Neonatal outcomes have been positive. CONCLUSION: ECMO should be considered a life-saving therapy for pregnant women with severe COVID-19.

Effectiveness of Tocilizumab in hospitalized moderate-to-severe COVID-19 patients: a real life study.

BACKGROUND: To assess the clinical effectiveness of Tocilizumab (TCZ) in moderate-to-severe hospitalized COVID-19 patients and factors associated with clinical response. METHODS: 508 inpatients with moderate-to-severe SARS-CoV-2 infection were enrolled. TCZ effect in addition to standard medical therapy was evaluated in terms of death during hospital stay. Unadjusted and adjusted risk of mortality for TCZ treated patients versus TCZ untreated ones was estimated using robust Cox regression model. We considered the combination of TCZ and ICU as time-dependent exposure and created a model using duplication method to assess the TCZ effect in very severe COVID-19 patients. RESULTS: TCZ REDUCED DEATH DURING HOSPITAL STAY IN THE UNADJUSTED MODEL (HR 0.54, 95%CI 0.33- 0.88) and also in the adjusted model, although with loss of statistical significance (HR 0.72, 0.43- 1.20). Better effectiveness was observed in patients with low SpO2/FiO2 ratio (HR 0.35, 0.21-0.61 vs 1.61, 0.54-4.82, p<0.05), and, without statistical significance, in patients with high CRP (HR 0.51, 0.30-0.87 vs 0.41, 0.12-1.37, p =NS) and high IL-6 (HR 0.49, 0.29-0.82 vs 1.00, 0.28-3.55, p=NS). TCZ was effective in patients not admitted to ICU, both in the unadjusted (HR 0.33, 0.14-0.74) and in the adjusted (HR 0.39, 0.17-0.91) model but no benefit was observed in critical ICU-admitted patients both in the unadjusted (HR 0.66, 0.37-1.15) and in the adjusted model (HR 0.95, 0.54-1.68). CONCLUSIONS: our real-life study suggests clinical efficacy of TCZ in moderate-to-severe COVID-19 patients but not in end-stage disease. Thus, to enhance TCZ effectiveness, patients should be selected before grave compromise of clinical conditions.

Effects of rescue inhaled nitric oxide on right ventricle and pulmonary circulation in severe COVID-related acute respiratory distress syndrome.

PURPOSES: To assess the effects of inhaled Nitric Oxide (iNO) on right ventricle dimension and function and systolic pulmonary arterial pressures in severe Acute Respiratory Distress (ARDS) due to Sars-Cov2 (COVID) infection. MATERIALS AND METHODS: We assessed the effects of iNO on right ventricle dimension and function and systolic pulmonary arterial pressures in 12 consecutive COVID-related ARDS patients by means of serial echocardiographic exams (baseline, 12 and 24 h since iNO start). RESULTS: Inhaled NO administration did not influence systolic pulmonary arterial pressures nor RV dimension and function. No changes were detectable in ventilatory data with iNO administration. Considering the negligible effect on oxygenation, iNO use was discontinued in all cases. CONCLUSIONS: In COVID-related severe ARDS iNO administrated as rescue therapy is not able to ameliorate oxygenation nor pulmonary hypertension, as assessed by serial echocardiograms. This finding may be explained by the diffuse loss of hypoxic pulmonary vasoconstriction with increased perfusion around alveolar consolidations which characterizes COVID-related severe ARDS.

Serum sodium alterations in SARS CoV-2 (COVID-19) infection: impact on patient outcome.

OBJECTIVE: Hyponatremia is the most common electrolyte disorder in hospitalized patients and occurs in about 30% of patients with pneumonia. Hyponatremia has been associated with a worse outcome in several pathologic conditions The main objective of this study was to determine whether serum sodium alterations may be independent predictors of the outcome of hospitalized COVID-19 patients. DESIGN AND METHODS: In this observational study, data from 441 laboratory-confirmed COVID-19 patients admitted to a University Hospital were collected. After excluding 61 patients (no serum sodium at admission available, saline solution infusion before sodium assessment, transfer from another hospital), data from 380 patients were analyzed. RESULTS: 274 (72.1%) patients had normonatremia at admission, 87 (22.9%) patients had hyponatremia and 19 (5%) patients had hypernatremia. We found an inverse correlation between serum sodium and IL-6, whereas a direct correlation between serum sodium and PaO2/FiO2 ratio was observed. Patients with hyponatremia had a higher prevalence of non-invasive ventilation and ICU transfer than those with normonatremia or hypernatremia. Hyponatremia was an independent predictor of in-hospital mortality (2.7-fold increase vs normonatremia) and each mEq/L of serum sodium reduction was associated with a 14.4% increased risk of death. CONCLUSIONS: These results suggest that serum sodium at admission may be considered as an early prognostic marker of disease severity in hospitalized COVID-19 patients.

Persistent Right Ventricle Dilatation in SARS-CoV-2-Related Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation Support.

OBJECTIVES: Venovenous extracorporeal membrane oxygenation (ECMO) support may be considered in experienced centers for patients with acute respiratory distress syndrome (ARDS) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection refractory to conventional treatment. In ECMO patients, echocardiography has emerged as a clinical tool for implantation and clinical management; but to date, little data are available on COVID-related ARDS patients requiring ECMO. The authors assessed the incidence of right ventricular dilatation and dysfunction (RvDys) in patients with COVID-related ARDS requiring ECMO. DESIGN: Single-center investigation. SETTING: Intensive care unit (ICU). PARTICIPANTS: A total of 35 patients with COVID-related ARDS requiring ECMO, consecutively admitted to the ICU (March 1, 2020, to February 28, 2021). INTERVENTIONS: Serial echocardiographic examinations. RvDys was defined as RV end-diastolic area/LV end-diastolic area >0.6 and tricuspid annular plane excursion <15 mm. MEASUREMENTS AND MAIN RESULTS: The incidence of RvDys was 15/35 (42%). RvDys patients underwent ECMO support after a longer period of mechanical ventilation (p = 0.006) and exhibited a higher mortality rate (p = 0.024) than those without RvDys. In nonsurvivors, RvDys was observed in all patients (n = nine) who died with unfavorable progression of COVID-related ARDS. In survivors, weaned from ECMO, a significant reduction in systolic pulmonary arterial pressures was detectable. CONCLUSIONS: According to the authors' data, in COVID-related ARDS requiring ECMO support, RvDys is common, associated with increased ICU mortality. Overall, the data underscored the clinical role of echocardiography in COVID-related ARDS supported by venovenous ECMO, because serial echocardiographic assessments (especially focused on RV changes) are able to reflect pulmonary COVID disease severity.

Epidemiological analysis of a COVID-19 outbreak associated with an infected surgeon.

Control of the novel COronaVIrus Disease-2019 (COVID-19) in a hospital setting is a priority. A COVID-19-infected surgeon performed surgical activities before being tested. An exposure risk classification was applied to the identified exposed subjects and high- and medium-risk contacts underwent active symptom monitoring for 14 days at home. All healthcare professionals (HCPs) were tested for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) at the end of the quarantine and serological tests were performed. Three household contacts and 20 HCPs were identified as high- or medium-risk contacts and underwent a 14-day quarantine. Fourteen HCPs and 19 patients were instead classified as low risk. All the contacts remained asymptomatic and all HCPs tested negative for SARS-CoV-2. About 25-28 days after their last exposure, HCPs underwent serological testing and two of them had positive IgM but negative confirmatory swabs. In a low COVID-19 burden area, the in-hospital transmission of SARS-CoV-2 from an infectious doctor did not occur and, despite multiple and frequent contacts, a hospital outbreak was avoided. This may be linked to the adoption of specific recommendations and to the use of standard personal protective equipment by HCPs.

Electrodiagnostic findings in patients with non-COVID-19- and COVID-19-related acute respiratory distress syndrome.

BACKGROUND: Critical illness polyneuropathy and myopathy (CIPNM) is a frequent neurological manifestation in patients with acute respiratory distress syndrome (ARDS) from coronavirus disease 2019 (COVID-19) infection. CIPNM diagnosis is usually limited to clinical evaluation. We compared patients with ARDS from COVID-19 and other aetiologies, in whom a neurophysiological evaluation for the detection of CIPNM was performed. The aim was to determine if there were any differences between these two groups in frequency of CINPM and outcome at discharge from the intensive care unit (ICU). MATERIALS AND METHODS: This was a single-centre retrospective study performed on mechanically ventilated patients consecutively admitted (January 2016-June 2020) to the ICU of Careggi Hospital, Florence, Italy, with ARDS of different aetiologies. Neurophysiological evaluation was performed on patients with stable ventilation parameters, but marked widespread hyposthenia (Medical Research Council score <48). Creatine phosphokinase (CPK), lactic dehydrogenase (LDH) and mean morning glycaemic values were collected. RESULTS: From a total of 148 patients, 23 with COVID-19 infection and 21 with ARDS due to other aetiologies, underwent electroneurography/electromyography (ENG/EMG) recording. Incidence of CIPNM was similar in the two groups, 65% (15 of 23) in COVID-19 patients and 71% (15 of 21) in patients affected by ARDS of other aetiologies. At ICU discharge, subjects with CIPNM more frequently required ventilatory support, regardless the aetiology of ARDS. CONCLUSION: ENG/EMG represents a useful tool in the identification of the neuromuscular causes underlying ventilator wean failure and patient stratification. A high incidence of CIPNM, with a similar percentage, has been observed in ARDS patients of all aetiologies.

The prognostic role of hyperglycemia and glucose variability in covid-related acute respiratory distress Syndrome.

AIMS: Due to heterogeneity on the prognostic role of glucose values and glucose variability in Novel Coronavirus (COVID) disease, we aimed at assessing the prognostic role for Intensive Care Unit (ICU) death of admission hyperglycaemia, peak glycemia and glucose variability in critically ill COVID patients: METHODS: 83 patients consecutively admitted for COVID-related Acute Respiratory Distress Syndrome (ARDS) from from 1st March to 1st October 2020. RESULTS: Non survivors were older, with more comorbidities and a more severe disease. Corticosteroids were used in the majority of patients (54/83, 65%) with no difference between survivors and non survivors. Mean blood glucose values, (during the first 24 and 48 h, respectively), were comparable between the two subgroups, as well as SD 24 and CV 24. During the first 48 h, survivors showed significantly lower values of SD 48 (p < 0.001) and CV 48, respectively (p < 0.001) than non survivors. CONCLUSIONS: in consecutive COVID-related ARDS patients admitted to ICU hyperglycemia (>180 mg/dl) is more common in non survivors who also showed a significantly higher glucose variability in the first 48 h since ICU admission. Our findings point to the clinical significance of in-ICU glucose control in severe COVID patients.

Combined lung and cardiac ultrasound in COVID-related acute respiratory distress syndrome.

BACKGROUND: Lung ultrasound (LU) is a useful tool for monitoring lung involvement in novel coronavirus (COVID) disease, while information on echocardiographic findings in COVID disease is to date scarce and heterogeneous. We hypothesized that lung and cardiac ultrasound examinations, serially and simultaneously performed, could monitor disease severity in COVID-related ARDS. METHODS: We enrolled 47 consecutive patients with COVID-related ARDS (1st March-31st May 2020). Lung and cardiac ultrasounds were performed on admission, at discharged and when clinically needed. RESULTS: Most patients were mechanically ventilated (75%) and veno-venous extracorporeal membrane oxygenation was needed in ten patients (21.2%). The in-ICU mortality rate was 27%%. On admission, not survivors showed a higher LUS score (p = 0.006) and a higher incidence of consolidations (p = 0.003), lower values of LVEF (p = 0.027) and a higher RV/LV ratio (0.008). At discharge, a significant reduction in the incidence of subpleural consolidations (p < 0.001) and, thus, in LUS score (p < 0.001) and an increase in patter A findings (p < 0.001) together with reduced systolic pulmonary arterial pressures were detectable. In not survivors at final examination, an increased in LUS score (p < 0.001), and in RV/LV ratio (p < 0.001) associated with a reduction in TAPSE (p = 0.013) were observed. A significant correlation was observed between LUS and systolic pulmonary arterial pressure (p = 0.04). LUS and RV/LV resulted independent predictors of in-ICU death. CONCLUSIONS: In COVID-related ARDS, the combined lung and cardiac ultrasound proved to be an useful clinical tool in monitoring disease progression and in identifying parameters (LU score and RV/LV ratio) able to risk stratifying these patients.

Metabolomic/lipidomic profiling of COVID-19 and individual response to tocilizumab.

The current pandemic emergence of novel coronavirus disease (COVID-19) poses a relevant threat to global health. SARS-CoV-2 infection is characterized by a wide range of clinical manifestations, ranging from absence of symptoms to severe forms that need intensive care treatment. Here, plasma-EDTA samples of 30 patients compared with age- and sex-matched controls were analyzed via untargeted nuclear magnetic resonance (NMR)-based metabolomics and lipidomics. With the same approach, the effect of tocilizumab administration was evaluated in a subset of patients. Despite the heterogeneity of the clinical symptoms, COVID-19 patients are characterized by common plasma metabolomic and lipidomic signatures (91.7% and 87.5% accuracy, respectively, when compared to controls). Tocilizumab treatment resulted in at least partial reversion of the metabolic alterations due to SARS-CoV-2 infection. In conclusion, NMR-based metabolomic and lipidomic profiling provides novel insights into the pathophysiological mechanism of human response to SARS-CoV-2 infection and to monitor treatment outcomes.