Corrigendum: Comfort during non-invasive ventilation.

[This corrects the article DOI: 10.3389/fmed.2022.874250.].

Monitoring of indoor bioaerosol for the detection of SARS-CoV-2 in different hospital settings.

Background: Spore Trap is an environmental detection technology, already used in the field of allergology to monitor the presence and composition of potentially inspirable airborne micronic bioparticulate. This device is potentially suitable for environmental monitoring of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in hospital, as well as in other high-risk closed environments. The aim of the present study is to investigate the accuracy of the Spore Trap system in detecting SARS-CoV-2 in indoor bioaerosol of hospital rooms. Methods: The Spore Trap was placed in hospital rooms hosting patients with documented SARS-CoV-2 infection (n = 36) or, as a negative control, in rooms where patients with documented negativity to a Real-Time Polymerase Chain Reaction molecular test for SARS-CoV-2 were admitted (n = 10). The monitoring of the bioaerosol was carried on for 24 h. Collected samples were analyzed by real-time polymerase chain reaction. Results: The estimated sensitivity of the Spore Trap device for detecting SARS-CoV-2 in an indoor environment is 69.4% (95% C.I. 54.3-84.4%), with a specificity of 100%. Conclusion: The Spore Trap technology is effective in detecting airborne SARS-CoV-2 virus with excellent specificity and high sensitivity, when compared to previous reports. The SARS-CoV-2 pandemic scenario has suggested that indoor air quality control will be a priority in future public health management and will certainly need to include an environmental bio-investigation protocol.

A platelet lipidomics signature in patients with COVID-19.

Ischemic cardiovascular and venous thromboembolic events are a frequent cause of death in severe COVID-19 patients. Platelet activation plays a key role in these complications, however platelet lipidomics have not been studied yet. The aim of our pilot investigation was to perform a preliminary study of platelet lipidomics in COVID-19 patients compared to healthy subjects. Lipid extraction and identification of ultrapurified platelets from eight hospitalized COVID-19 patients and eight age- and sex-matched healthy controls showed a lipidomic pattern almost completely separating COVID-19 patients from healthy controls. In particular, a significant decrease of ether phospholipids and increased levels of ganglioside GM3 were observed in platelets from COVID-19 patients. In conclusion, our study shows for the first time that platelets from COVID-19 patients display a different lipidomics signature distinguishing them from healthy controls, and suggests that altered platelet lipid metabolism may play a role in viral spreading and in the thrombotic complications of COVID-19.

What is the context? Besides respiratory system involvement, venous thromboembolism is a severe complication of COVID-19, largely due to the strong derangement of hemostasis, with platelets playing a central role.Great attention has recently been devoted to lipid alterations in COVID-19, both because viruses by reprogramming cellular lipid metabolism remodel lipid membranes to fuel their replication, and because the COVID-19-associated cytokine storm may affect cell/plasma lipidomic signatures.Lipidomics studies in COVID-19 patients have been performed mainly in plasma and serum.To the best of our knowledge, platelet lipidomics have not been examined despite the central role played by platelets in COVID-19 complications.What is the aim of the study?The aim of our pilot study was to preliminarily explore whether platelet lipidomics is altered in COVID-19 patients compared to age- and sex-matched healthy subjects, analyzing lipidomic profile of ultrapurified platelets.What are the results of our study? Our study shows for the first time that platelets from COVID-19 patients display a different lipidomics signature distinguishing them from healthy controls.Ether phospholipids and, intriguingly, two phytoceramides were lower, while ganglioside GM3 was higher in COVID-19 samples compared to healthy controls.What is the impact?Despite the small number of COVID-19 patients enrolled, recognized as a limitation of our study, we show, for the first time, that platelets from COVID-19 patients present a different lipidomics signature and suggest that altered platelet lipid metabolism may play a significant role in viral spreading and in the thrombotic complications of COVID-19.

Comfort During Non-invasive Ventilation.

Non-invasive ventilation (NIV) has been shown to be effective in avoiding intubation and improving survival in patients with acute hypoxemic respiratory failure (ARF) when compared to conventional oxygen therapy. However, NIV is associated with high failure rates due, in most cases, to patient discomfort. Therefore, increasing attention has been paid to all those interventions aimed at enhancing patient's tolerance to NIV. Several practical aspects have been considered to improve patient adaptation. In particular, the choice of the interface and the ventilatory setting adopted for NIV play a key role in the success of respiratory assistance. Among the different NIV interfaces, tolerance is poorest for the nasal and oronasal masks, while helmet appears to be better tolerated, resulting in longer use and lower NIV failure rates. The choice of fixing system also significantly affects patient comfort due to pain and possible pressure ulcers related to the device. The ventilatory setting adopted for NIV is associated with varying degrees of patient comfort: patients are more comfortable with pressure-support ventilation (PSV) than controlled ventilation. Furthermore, the use of electrical activity of the diaphragm (EADi)-driven ventilation has been demonstrated to improve patient comfort when compared to PSV, while reducing neural drive and effort. If non-pharmacological remedies fail, sedation can be employed to improve patient's tolerance to NIV. Sedation facilitates ventilation, reduces anxiety, promotes sleep, and modulates physiological responses to stress. Judicious use of sedation may be an option to increase the chances of success in some patients at risk for intubation because of NIV intolerance consequent to pain, discomfort, claustrophobia, or agitation. During the Coronavirus Disease-19 (COVID-19) pandemic, NIV has been extensively employed to face off the massive request for ventilatory assistance. Prone positioning in non-intubated awake COVID-19 patients may improve oxygenation, reduce work of breathing, and, possibly, prevent intubation. Despite these advantages, maintaining prone position can be particularly challenging because poor comfort has been described as the main cause of prone position discontinuation. In conclusion, comfort is one of the major determinants of NIV success. All the strategies aimed to increase comfort during NIV should be pursued.

Effect of Immuno-Nutrition on Malnutrition, Inflammatory Response and Clinical Course of Semi-Critically Ill COVID-19 Patients: A Pilot Perspective Study

Background: The SARS-COV 2 pandemic has hit on our lives since early 2020. During different contagion waves, both malnutrition and overweight significantly correlated with patient mortality. Immune-nutrition (IN) has shown promising results in the clinical course of pediatric inflammatory bowel disease (IBD) and in both the rate of extubation and mortality of patients admitted to an intensive care unit (ICU). Thus, we wanted to assess the effects of IN on a clinical course of patients admitted to a semi-intensive COVID-19 Unit during the fourth wave of contagion that occurred at the end of 2021. Methods: we prospectively enrolled patients admitted to the semi-intensive COVID-19 Unit of San Benedetto General hospital. All patients had a biochemical, anthropometric, high-resolution tomography chest scan (HRCT) and complete nutritional assessments at the time of admission, after oral administration of immune-nutrition (IN) formula, and at 15 days interval follow-up. Results: we enrolled 34 consecutive patients (age 70.3 ± 5.4 years, 6 F, BMI 27.0 ± 0.5 kg/m2). Main comorbidities were diabetes (20%, type 2 90 %), hyperuricemia (15%), hypertension (38%), chronic ischemic heart disease (8 %), COPD (8%), anxiety syndrome (5%), and depression (5%). 58% of patients were affected as moderately-to-severely overweight;mini nutritional assessment (MNA) score (4.8 ± 0.7) and phase angle (PA) values (3.8 ± 0.5) suggestive of malnutrition were present in 15% of patients, mainly with a history of cancer. After 15 days upon admission, we recorded 3 deaths (mean age 75.7 ± 5.1 years, BMI 26.3 ± 0.7 kg/m2) and 4 patients were admitted to the ICU. Following IN formula administration, inflammatory markers significantly decreased (p < 0.05) while BMI and PA did not worsen. These latter findings were not observed in a historical control group that did not receive IN. Only one patient needed protein-rich formula administration. Conclusions: in this overweight COVID-19 population immune-nutrition prevented malnutrition development with a significant decrease of inflammatory markers.

Treatment of patients with 'do not intubate orders'.

PURPOSE OF REVIEW: Do-not-intubate (DNI) orders are more frequently encountered over time. This widespread diffusion of DNI orders make it essential to develop therapeutic strategies matching patient's and his family willingness. The present review sheds light on the therapeutic approaches employed to support respiratory function of patients with DNI orders. RECENT FINDINGS: In DNI patients, several approaches have been described to relieve dyspnoea and address acute respiratory failure (ARF). Despite its extensive use, supplemental oxygen is not so useful in assuring dyspnoea relief. Noninvasive respiratory support (NIRS) is frequently employed to treat ARF in DNI patients. Also, to enhance DNI patients comfort during NIRS, it is worthy to point out the role of analgo-sedative medications. Lastly, a particular aspect concerns the first waves of coronavirus disease 2019 pandemic, when DNI orders have been pursued on factors unrelated to patient's wishes, in the total absence of family support due to the lockdown policy. In this setting, NIRS has been extensively employed in DNI patients with a survival rate of around 20%. SUMMARY: In dealing with DNI patients, the individualization of treatments is of pivotal importance to respect patient's preferences and improve quality of life at the same time.

Effect of Immuno-Nutrition on Malnutrition, Inflammatory Response and Clinical Course of Semi-Critically Ill COVID-19 Patients: A Pilot Perspective Study.

BACKGROUND: The SARS-COV 2 pandemic has hit on our lives since early 2020. During different contagion waves, both malnutrition and overweight significantly correlated with patient mortality. Immune-nutrition (IN) has shown promising results in the clinical course of pediatric inflammatory bowel disease (IBD) and in both the rate of extubation and mortality of patients admitted to an intensive care unit (ICU). Thus, we wanted to assess the effects of IN on a clinical course of patients admitted to a semi-intensive COVID-19 Unit during the fourth wave of contagion that occurred at the end of 2021. METHODS: we prospectively enrolled patients admitted to the semi-intensive COVID-19 Unit of San Benedetto General hospital. All patients had a biochemical, anthropometric, high-resolution tomography chest scan (HRCT) and complete nutritional assessments at the time of admission, after oral administration of immune-nutrition (IN) formula, and at 15 days interval follow-up. RESULTS: we enrolled 34 consecutive patients (age 70.3 ± 5.4 years, 6 F, BMI 27.0 ± 0.5 kg/m2). Main comorbidities were diabetes (20%, type 2 90 %), hyperuricemia (15%), hypertension (38%), chronic ischemic heart disease (8 %), COPD (8%), anxiety syndrome (5%), and depression (5%). 58% of patients were affected as moderately-to-severely overweight; mini nutritional assessment (MNA) score (4.8 ± 0.7) and phase angle (PA) values (3.8 ± 0.5) suggestive of malnutrition were present in 15% of patients, mainly with a history of cancer. After 15 days upon admission, we recorded 3 deaths (mean age 75.7 ± 5.1 years, BMI 26.3 ± 0.7 kg/m2) and 4 patients were admitted to the ICU. Following IN formula administration, inflammatory markers significantly decreased (p < 0.05) while BMI and PA did not worsen. These latter findings were not observed in a historical control group that did not receive IN. Only one patient needed protein-rich formula administration. CONCLUSIONS: in this overweight COVID-19 population immune-nutrition prevented malnutrition development with a significant decrease of inflammatory markers.

Ventilatory associated barotrauma in COVID-19 patients: A multicenter observational case control study (COVI-MIX-study).

BACKGROUND: The risk of barotrauma associated with different types of ventilatory support is unclear in COVID-19 patients. The primary aim of this study was to evaluate the effect of the different respiratory support strategies on barotrauma occurrence; we also sought to determine the frequency of barotrauma and the clinical characteristics of the patients who experienced this complication. METHODS: This multicentre retrospective case-control study from 1 March 2020 to 28 February 2021 included COVID-19 patients who experienced barotrauma during hospital stay. They were matched with controls in a 1:1 ratio for the same admission period in the same ward of treatment. Univariable and multivariable logistic regression (OR) were performed to explore which factors were associated with barotrauma and in-hospital death. RESULTS: We included 200 cases and 200 controls. Invasive mechanical ventilation was used in 39.3% of patients in the barotrauma group, and in 20.1% of controls (p<0.001). Receiving non-invasive ventilation (C-PAP/PSV) instead of conventional oxygen therapy (COT) increased the risk of barotrauma (OR 5.04, 95% CI 2.30 - 11.08, p<0.001), similarly for invasive mechanical ventilation (OR 6.24, 95% CI 2.86-13.60, p<0.001). High Flow Nasal Oxygen (HFNO), compared with COT, did not significantly increase the risk of barotrauma. Barotrauma frequency occurred in 1.00% [95% CI 0.88-1.16] of patients; these were older (p=0.022) and more frequently immunosuppressed (p=0.013). Barotrauma was shown to be an independent risk for death (OR 5.32, 95% CI 2.82-10.03, p<0.001). CONCLUSIONS: C-PAP/PSV compared with COT or HFNO increased the risk of barotrauma; otherwise HFNO did not. Barotrauma was recorded in 1.00% of patients, affecting mainly patients with more severe COVID-19 disease. Barotrauma was independently associated with mortality. TRIAL REGISTRATION: this case-control study was prospectively registered in clinicaltrial.gov as NCT04897152 (on 21 May 2021).

Quality of Life in COVID-Related ARDS Patients One Year after Intensive Care Discharge (Odissea Study): A Multicenter Observational Study.

BACKGROUND: Investigating the health-related quality of life (HRQoL) after intensive care unit (ICU) discharge is necessary to identify possible modifiable risk factors. The primary aim of this study was to investigate the HRQoL in COVID-19 critically ill patients one year after ICU discharge. METHODS: In this multicenter prospective observational study, COVID-19 patients admitted to nine ICUs from 1 March 2020 to 28 February 2021 in Italy were enrolled. One year after ICU discharge, patients were required to fill in short-form health survey 36 (SF-36) and impact of event-revised (IES-R) questionnaire. A multivariate linear or logistic regression analysis to search for factors associated with a lower HRQoL and post-traumatic stress disorded (PTSD) were carried out, respectively. RESULTS: Among 1003 patients screened, 343 (median age 63 years [57-70]) were enrolled. Mechanical ventilation lasted for a median of 10 days [2-20]. Physical functioning (PF 85 [60-95]), physical role (PR 75 [0-100]), emotional role (RE 100 [33-100]), bodily pain (BP 77.5 [45-100]), social functioning (SF 75 [50-100]), general health (GH 55 [35-72]), vitality (VT 55 [40-70]), mental health (MH 68 [52-84]) and health change (HC 50 [25-75]) describe the SF-36 items. A median physical component summary (PCS) and mental component summary (MCS) scores were 45.9 (36.5-53.5) and 51.7 (48.8-54.3), respectively, considering 50 as the normal value of the healthy general population. In all, 109 patients (31.8%) tested positive for post-traumatic stress disorder, also reporting a significantly worse HRQoL in all SF-36 domains. The female gender, history of cardiovascular disease, liver disease and length of hospital stay negatively affected the HRQoL. Weight at follow-up was a risk factor for PTSD (OR 1.02, p = 0.03). CONCLUSIONS: The HRQoL in COVID-19 ARDS (C-ARDS) patients was reduced regarding the PCS, while the median MCS value was slightly above normal. Some risk factors for a lower HRQoL have been identified, the presence of PTSD is one of them. Further research is warranted to better identify the possible factors affecting the HRQoL in C-ARDS.

Lung ultrasound to evaluate aeration changes in response to recruitment maneuver and prone positioning in intubated patients with COVID-19 pneumonia: preliminary study.

BACKGROUND: This single-center preliminary prospective observational study used bedside ultrasound to assess the lung aeration modifications induced by recruitment maneuver and pronation in intubated patients with acute respiratory disease syndrome (ARDS) related to coronavirus 2019 disease (COVID-19). All adult intubated COVID-19 patients suitable for pronation were screened. After enrollment, patients underwent 1 h in a volume-controlled mode in supine position (baseline) followed by a 35-cmH2O-recruitment maneuver of 2 min (recruitment). Final step involved volume-controlled mode in prone position set as at baseline (pronation). At the end of the first two steps and 1 h after pronation, a lung ultrasound was performed, and global and regional lung ultrasound score (LUS) were analyzed. Data sets are presented as a median and 25th-75th percentile. RESULTS: From January to May 2022, 20 patients were included and analyzed. Global LUS reduced from 26.5 (23.5-30.0) at baseline to 21.5 (18.0-23.3) and 23.0 (21.0-26.3) at recruitment (p < 0.001) and pronation (p = 0.004). In the anterior lung regions, the regional LUS were 1.8 (1.1-2.0) following recruitment and 2.0 (1.6-2.2) in the supine (p = 0.008) and 2.0 (1.8-2.3) in prone position (p = 0.023). Regional LUS diminished from 2.3 (2.0-2.5) in supine to 2.0 (1.8-2.0) with recruitment in the lateral lung zones (p = 0.036). Finally, in the posterior lung units, regional LUS improved from 2.5 (2.3-2.8) in supine to 2.3 (1.8-2.5) through recruitment (p = 0.003) and 1.8 (1.3-2.2) with pronation (p < 0.0001). CONCLUSIONS: In our investigation, recruitment maneuver and prone positioning demonstrated an enhancement in lung aeration when compared to supine position, as assessed by bedside lung ultrasound. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , Number NCT05209477, prospectively registered and released on 01/26/2022.

Level of Diffusion and Training of Lung Ultrasound during the COVID-19 Pandemic - A National Online Italian Survey (ITALUS) from the Lung Ultrasound Working Group of the Italian Society of Anesthesia, Analgesia, Resuscitation, and Intensive Care (SIAARTI).

PURPOSE: The goal of this survey was to describe the use and diffusion of lung ultrasound (LUS), the level of training received before and during the COVID-19 pandemic, and the clinical impact LUS has had on COVID-19 cases in intensive care units (ICU) from February 2020 to May 2020. MATERIALS AND METHODS: The Italian Lung Ultrasound Survey (ITALUS) was a nationwide online survey proposed to Italian anesthesiologists and intensive care physicians carried out after the first wave of the COVID-19 pandemic. It consisted of 27 questions, both quantitative and qualitative. RESULTS: 807 responded to the survey. The median previous LUS experience was 3 years (IQR 1.0-6.0). 473 (60.9 %) reported having attended at least one training course on LUS before the COVID-19 pandemic. 519 (73.9 %) reported knowing how to use the LUS score. 404 (52 %) reported being able to use LUS without any supervision. 479 (68.2 %) said that LUS influenced their clinical decision-making, mostly with respect to patient monitoring. During the pandemic, the median of patients daily evaluated with LUS increased 3-fold (p < 0.001), daily use of general LUS increased from 10.4 % to 28.9 % (p < 0.001), and the daily use of LUS score in particular increased from 1.6 % to 9.0 % (p < 0.001). CONCLUSION: This survey showed that LUS was already extensively used during the first wave of the COVID-19 pandemic by anesthesiologists and intensive care physicians in Italy, and then its adoption increased further. Residency programs are already progressively implementing LUS teaching. However, 76.7 % of the sample did not undertake any LUS certification.

Krebs von den Lungen 6 (KL-6) levels in COVID-19 ICU patients are associated with mortality

Background Krebs von den Lungen 6 (KL-6) is a high-molecular-weight mucin-like glycoprotein, which is also known as MUC1. KL-6 is mainly produced by type 2 pneumocytes and bronchial epithelial cells, and, therefore, elevated circulating KL-6 levels may denote disorders of the alveolar epithelial lining. The objective of this study is to verify if KL-6 serum level might support ICU physicians in predicting mortality, risk stratifying and triaging severe COVID-19 patients. Methods A retrospective cohort study, including all the COVID-19 patients who measured KL-6 serum values at least once during their ICU stay, was performed. The study sample, 122 patients, was divided in two groups, according to the median KL-6 value at ICU admission (median log-transformed KL-6 value: 6.73 U/ml;group A: KL-6 lower than the median and group B: KL-6 higher than the median). Results One-hundred twenty-two ICU patients were included in this study. Mortality was higher in group B than in group A (80 versus 46%;p < 0.001);both linear and logistic multivariate analyses showed ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (P/F) significantly and inversely related to KL-6 values. Conclusion At ICU admission, KL-6 serum level was significantly higher in the most hypoxic COVID-19 patients and independently associated with ICU mortality.

Potential of FX06 to prevent disease progression in hospitalized non-intubated COVID-19 patients - the randomized, EU-wide, placebo-controlled, phase II study design of IXION.

BACKGROUND: More than 2.7 million hospitalizations of COVID-19-infected patients have occurred in Europe alone since the outbreak of the coronavirus in 2020. Interventions against SARS-CoV-2 are still in high need to prevent admissions to ICUs worldwide. FX06, a naturally occurring peptide in humans and other mammals, has the potential to reduce capillary leak by improving endothelial dysfunction and thus preventing the deterioration of patients. With IXION, we want to investigate the potential of FX06 to prevent disease progression in hospitalized, non-intubated COVID-19 patients. METHODS: IXION is an EU-wide, multicentre, placebo-controlled, double-blinded, parallel, randomized (2:1) phase II clinical study. Patient recruitment will start in September 2022 (to Q2/2023) in Germany, Italy, Lithuania, Spain, Romania, Portugal, and France. A total of 306 hospitalized patients (≥ 18 years and < 75 years) with a positive SARS-CoV-2 PCR test and a COVID-19 severity of 4-6 according to the WHO scale will be enrolled. After randomization to FX06 or placebo, patients will be assessed until day 28 (and followed up until day 60). FX06 (2 × 200 mg per day) or placebo will be administered intravenously for 5 consecutive days. The primary endpoint is to demonstrate a difference in the proportion of patients with progressed/worsened disease state in patients receiving FX06 compared to patients receiving placebo. Secondary endpoints are lung function, oxygen saturation and breathing rate, systemic inflammation, survival, capillary refill time, duration of hospital stay, and drug accountability. DISCUSSION: With IXION, the multidisciplinary consortium aims to deliver a new therapy in addition to standard care against SARS-CoV-2 for the clinical management of COVID-19 during mild and moderate stages. Potential limitations might refer to a lack of recruiting and drop-out due to various possible protocol violations. While we controlled for drop-outs in the same size estimation, recruitment problems may be subject to external problems difficult to control for. TRIAL REGISTRATION: EudraCT 2021-005059-35 . Registered on 12 December 2021. Study Code TMP-2204-2021-47.

Diaphragm ultrasound evaluation during weaning from mechanical ventilation in COVID-19 patients: a pragmatic, cross-section, multicenter study.

BACKGROUND: Diaphragmatic dysfunction is a major factor responsible for weaning failure in patients that underwent prolonged invasive mechanical ventilation for acute severe respiratory failure from COVID-19. This study hypothesizes that ultrasound measured diaphragmatic thickening fraction (DTF) could provide corroborating information for weaning COVID-19 patients from mechanical ventilation. METHODS: This was an observational, pragmatic, cross-section, multicenter study in 6 Italian intensive care units. DTF was assessed in COVID-19 patients undergoing weaning from mechanical ventilation from 1st March 2020 to 30th June 2021. Primary aim was to evaluate whether DTF is a predictive factor for weaning failure. RESULTS: Fifty-seven patients were enrolled, 25 patients failed spontaneous breathing trial (44%). Median length of invasive ventilation was 14 days (IQR 7-22). Median DTF within 24 h since the start of weaning was 28% (IQR 22-39%), RASS score (- 2 vs - 2; p = 0.031); Kelly-Matthay score (2 vs 1; p = 0.002); inspiratory oxygen fraction (0.45 vs 0.40; p = 0.033). PaO2/FiO2 ratio was lower (176 vs 241; p = 0.032) and length of intensive care stay was longer (27 vs 16.5 days; p = 0.025) in patients who failed weaning. The generalized linear regression model did not select any variables that could predict weaning failure. DTF was correlated with pH (RR 1.56 × 1027; p = 0.002); Kelly-Matthay score (RR 353; p < 0.001); RASS (RR 2.11; p = 0.003); PaO2/FiO2 ratio (RR 1.03; p = 0.05); SAPS2 (RR 0.71; p = 0.005); hospital and ICU length of stay (RR 1.22 and 0.79, respectively; p < 0.001 and p = 0.004). CONCLUSIONS: DTF in COVID-19 patients was not predictive of weaning failure from mechanical ventilation, and larger studies are needed to evaluate it in clinical practice further. Registered: ClinicalTrial.gov (NCT05019313, 24 August 2021).

Potential of FX06 to prevent disease progression in hospitalized non-intubated COVID-19 patients — the randomized, EU-wide, placebo-controlled, phase II study design of IXION

Background More than 2.7 million hospitalizations of COVID-19-infected patients have occurred in Europe alone since the outbreak of the coronavirus in 2020. Interventions against SARS-CoV-2 are still in high need to prevent admissions to ICUs worldwide. FX06, a naturally occurring peptide in humans and other mammals, has the potential to reduce capillary leak by improving endothelial dysfunction and thus preventing the deterioration of patients. With IXION, we want to investigate the potential of FX06 to prevent disease progression in hospitalized, non-intubated COVID-19 patients. Methods IXION is an EU-wide, multicentre, placebo-controlled, double-blinded, parallel, randomized (2:1) phase II clinical study. Patient recruitment will start in September 2022 (to Q2/2023) in Germany, Italy, Lithuania, Spain, Romania, Portugal, and France. A total of 306 hospitalized patients (≥ 18 years and < 75 years) with a positive SARS-CoV-2 PCR test and a COVID-19 severity of 4–6 according to the WHO scale will be enrolled. After randomization to FX06 or placebo, patients will be assessed until day 28 (and followed up until day 60). FX06 (2 × 200 mg per day) or placebo will be administered intravenously for 5 consecutive days. The primary endpoint is to demonstrate a difference in the proportion of patients with progressed/worsened disease state in patients receiving FX06 compared to patients receiving placebo. Secondary endpoints are lung function, oxygen saturation and breathing rate, systemic inflammation, survival, capillary refill time, duration of hospital stay, and drug accountability. Discussion With IXION, the multidisciplinary consortium aims to deliver a new therapy in addition to standard care against SARS-CoV-2 for the clinical management of COVID-19 during mild and moderate stages. Potential limitations might refer to a lack of recruiting and drop-out due to various possible protocol violations. While we controlled for drop-outs in the same size estimation, recruitment problems may be subject to external problems difficult to control for. Trial registration EudraCT 2021-005059-35. Registered on 12 December 2021. Study Code TMP-2204-2021-47. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-022-06609-x.

Noninvasive respiratory support outside the intensive care unit for acute respiratory failure related to coronavirus-19 disease: a systematic review and meta-analysis.

BACKGROUND: Noninvasive respiratory support (NIRS) has been diffusely employed outside the intensive care unit (ICU) to face the high request of ventilatory support due to the massive influx of patients with acute respiratory failure (ARF) caused by coronavirus-19 disease (COVID-19). We sought to summarize the evidence on clinically relevant outcomes in COVID-19 patients supported by NIV outside the ICU. METHODS: We searched PUBMED®, EMBASE®, and the Cochrane Controlled Clinical trials register, along with medRxiv and bioRxiv repositories for pre-prints, for observational studies and randomized controlled trials, from inception to the end of February 2021. Two authors independently selected the investigations according to the following criteria: (1) observational study or randomized clinical trials enrolling ≥ 50 hospitalized patients undergoing NIRS outside the ICU, (2) laboratory-confirmed COVID-19, and (3) at least the intra-hospital mortality reported. Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines were followed. Data extraction was independently performed by two authors to assess: investigation features, demographics and clinical characteristics, treatments employed, NIRS regulations, and clinical outcomes. Methodological index for nonrandomized studies tool was applied to determine the quality of the enrolled studies. The primary outcome was to assess the overall intra-hospital mortality of patients under NIRS outside the ICU. The secondary outcomes included the proportions intra-hospital mortalities of patients who underwent invasive mechanical ventilation following NIRS failure and of those with 'do-not-intubate' (DNI) orders. RESULTS: Seventeen investigations (14 peer-reviewed and 3 pre-prints) were included with a low risk of bias and a high heterogeneity, for a total of 3377 patients. The overall intra-hospital mortality of patients receiving NIRS outside the ICU was 36% [30-41%]. 26% [21-30%] of the patients failed NIRS and required intubation, with an intra-hospital mortality rising to 45% [36-54%]. 23% [15-32%] of the patients received DNI orders with an intra-hospital mortality of 72% [65-78%]. Oxygenation on admission was the main source of between-study heterogeneity. CONCLUSIONS: During COVID-19 outbreak, delivering NIRS outside the ICU revealed as a feasible strategy to cope with the massive demand of ventilatory assistance. REGISTRATION: PROSPERO, https://www.crd.york.ac.uk/prospero/ , CRD42020224788, December 11, 2020.

What's new on the management of obstetric patients who tested positive for COVID-19?

To date, there is still partial data on the effects of COVID-19 on pregnant women. The constant collection of information results in a continuous updating of the knowledge about the best management of pregnant patients affected by COVID-19. This work aimed to summarize the state of the art on prevention and management of SARS-CoV-2 infection in obstetric patients. This was enabled by a comprehensive literature search for the most recent and relevant publications on the subject, including guidelines and recommendations. Management of these women by a multidisciplinary team is of crucial importance, given the extreme clinical complexity of this condition. Every health worker involved must put in place all possible procedures to protect themselves from contagion. Neuraxial anesthesia should be favored in the management of labor and caesarean section over other modalities, unless there are contraindications based on the patient's status. There is still no standardized drug treatment in pregnant women with COVID-19 due to their exclusion from studies conducted to evaluate pharmacological therapies. Nevertheless, various drugs have been used to treat this disease in pregnancy, although the data at our disposal are still few. As regards mRNA vaccines, it seems that their immunogenicity, safety and tolerability in pregnant women are comparable to those of non-pregnant women of the same age. More studies are certainly needed in infected pregnant women to establish treatment and prevention protocols for this special category of patients.

Effect of Whey Proteins on Malnutrition and Extubating Time of Critically Ill COVID-19 Patients.

The novel SARS-CoV-2 virus has led to a severe pandemic, starting from early 2020. Intensive care (ICU) management of the COVID-19 disease is difficult with high morbidity and mortality. Early nutritional support, especially with whey protein, seems to be crucial in this medical case. Thus, we aimed to assess the effects of an adequate nutritional protocol rich in whey protein on nutritional and inflammatory status, extubating time, and mortality of critically ill COVID-19 patients (CICP). METHODS: A prospective single-center exploratory observational study was undertaken on 32 consecutive CICP admitted to the ICU of Santa Maria Hospital, Terni, Italy, and treated with whey protein-enriched formula. Patients' demographics, nutritional status, indexes of inflammation, daily pre-albumin serum levels, duration of mechanical ventilation, and mortality were recorded. RESULTS: Thirty-two patients were enrolled. Ninety-five percent of them showed a gradual reduction in C-reactive protein (CRP) values and increase in pre-albumin levels after the whey protein-enriched formula. Prealbumin levels were not correlated with a better nutritional status but with a shorter extubating time and better survival. CONCLUSIONS: An adequate administration of whey protein during COVID-19 patients' ICU stays can provide fast achievement of protein targets, reducing the duration of mechanical ventilation, and improving inflammatory status and ICU survival. Further prospective and large-scale, controlled studies are needed to confirm these results.