Barotrauma during Noninvasive Respiratory Support in COVID-19 Pneumonia Outside ICU: The Ancillary COVIMIX-2 Study.

BACKGROUND: Noninvasive respiratory support (NIRS) has been extensively used during the COVID-19 surge for patients with acute respiratory failure. However, little data are available about barotrauma during NIRS in patients treated outside the intensive care unit (ICU) setting. METHODS: COVIMIX-2 was an ancillary analysis of the previous COVIMIX study, a large multicenter observational work investigating the frequencies of barotrauma (i.e., pneumothorax and pneumomediastinum) in adult patients with COVID-19 interstitial pneumonia. Only patients treated with NIRS outside the ICU were considered. Baseline characteristics, clinical and radiological disease severity, type of ventilatory support used, blood tests and mortality were recorded. RESULTS: In all, 179 patients were included, 60 of them with barotrauma. They were older and had lower BMI than controls (p < 0.001 and p = 0.045, respectively). Cases had higher respiratory rates and lower PaO2/FiO2 (p = 0.009 and p < 0.001). The frequency of barotrauma was 0.3% [0.1-1.3%], with older age being a risk factor for barotrauma (OR 1.06, p = 0.015). Alveolar-arterial gradient (A-a) DO2 was protective against barotrauma (OR 0.92 [0.87-0.99], p = 0.026). Barotrauma required active treatment, with drainage, in only a minority of cases. The type of NIRS was not explicitly related to the development of barotrauma. Still, an escalation of respiratory support from conventional oxygen therapy, high flow nasal cannula to noninvasive respiratory mask was predictive for in-hospital death (OR 15.51, p = 0.001). CONCLUSIONS: COVIMIX-2 showed a low frequency for barotrauma, around 0.3%. The type of NIRS used seems not to increase this risk. Patients with barotrauma were older, with more severe systemic disease, and showed increased mortality.

Lung ultrasound monitoring: impact on economics and outcomes.

PURPOSE OF REVIEW: This review aims to summarize the impact of lung ultrasonography (LUS) on economics and possible impact on patients' outcomes, proven its diagnostic accuracy in patients with acute respiratory failure. RECENT FINDINGS: Despite some previous ethical concerns on LUS examination, today this technique has showed several advantages. First, it is now clear that the daily use of LUS can provide a relevant cost reduction in healthcare of patients with acute respiratory failure, while reducing the risk of transport of patients to radiological departments for chest CT scan. In addition, LUS reduces the exposition to x-rays since can replace the bedside chest X-ray examination in many cases. Indeed, LUS is characterized by a diagnostic accuracy that is even superior to portable chest X-ray when performed by well trained personnel. Finally, LUS examination is a useful tool to predict the course of patients with pneumonia, including the need for hospitalization and ICU admission, noninvasive ventilation failure and orotracheal intubation, weaning success, and mortality. SUMMARY: LUS should be implemented not only in Intensive Care Units, but also in other setting like emergency departments. Since most data comes from the recent coronavirus disease 2019 pandemic, further investigations are required in Acute Respiratory Failure of different etiologies.

Severe and mild-moderate SARS-CoV-2 vaccinated patients show different frequencies of IFNγ-releasing cells: An exploratory study.

BACKGROUND: Despite an apparent effective vaccination, some patients are admitted to the hospital after SARS-CoV-2 infection. The role of adaptive immunity in COVID-19 is growing; nonetheless, differences in the spike-specific immune responses between patients requiring or not hospitalization for SARS-CoV-2 infection remains to be evaluated. In this study, we aim to evaluate the spike-specific immune response in patients with mild-moderate or severeSARS-CoV-2 infection, after breakthrough infection following two doses of BNT162b2 mRNA vaccine. METHODS: We included three cohorts of 15 cases which received the two BNT162b2 vaccine doses in previous 4 to 7 months: 1) patients with severe COVID-19; 2) patients with mild-moderate COVID-19 and 3) vaccinated individuals with a negative SARS-CoV-2 molecular pharyngeal swab (healthy subjects). Anti-S1 and anti-S2 specific SARS-CoV-2 IgM and IgG titers were measured through a chemiluminescence immunoassay technology. In addition, the frequencies of IFNγ-releasing cells were measured by ELISpot. RESULTS: The spike-specific IFNγ-releasing cells were significantly lower in severe patients (8 [0; 26] s.f.c.×106), as compared to mild-moderate patients (135 [64; 159] s.f.c.×106; p<0.001) and healthy subjects (103 [50; 188] s.f.c.×106; p<0.001). The anti-Spike protein IgG levels were similar among the three cohorts of cases (p = 0.098). All cases had an IgM titer below the analytic sensitivity of the test. The Receiver Operating Curve analysis indicated the rate of spike-specific IFNγ-releasing cells can discriminate correctly severe COVID-19 and mild-moderate patients (AUC: 0.9289; 95%CI: 0.8376-1.000; p< 0.0001), with a diagnostic specificity of 100% for s.f.c. > 81.2 x 106. CONCLUSIONS: 2-doses vaccinated patients requiring hospitalization for severe COVID-19 show a cellular-mediated immune response lower than mild-moderate or healthy subjects, despite similar antibody titers.

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.

Characteristics of unvaccinated and vaccinated critically ill COVID-19 patients in calabria region (Italy): A retrospective study.

Introduction: After the rapid surge of a novel coronavirus (SARS-CoV-2) in 2020 anti-SARS-CoV-2 vaccines have been developed to prevent the development of critical forms of COVID-19 leading to Intensive Care Unit (ICU) admission. The possibility of ICU admission after the first-cycle vaccination has been already reported; however, no data have been published regarding vaccinated patients with a "booster" dose. This retrospective study describes the characteristics of critically ill patients after the implementation of the regional "booster" dose vaccination program in a southern region of Italy. Materials and methods: We screened all medical records of critically ill COVID-19 patients in the period between January to April 2022. We collected the demographic characteristics, the presence of comorbidities, the vaccination status, the clinical course (arterial blood gases and type of respiratory support) and outcomes (rate of tracheostomy, ICU length of stay and mortality). Results: A total of 272 patients were admitted to ICUs during the study period. 161 patients were unvaccinated, whereas 111 were vaccinated with the complete first-cycle or "booster" dose. The type of respiratory support was similar between groups. Vaccinated patients were characterized by a better oxygenation throughout the whole ICU length of stay. Fourteen unvaccinated and 3 vaccinated patients required tracheostomy (p = 0.045). ICU length of stay was 12.2 (± 7.3) days in unvaccinated patients and 10.4 (± 6.7) days in vaccinated patients (p = 0.036). ICU mortalities were 38.5 and 24.3% in unvaccinated and vaccinated patients, respectively (p = 0.014). Conclusion: Vaccinated patients have better clinical course and outcomes as compared to the unvaccinated population.

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).

Bivalirudin vs. Enoxaparin in Intubated COVID-19 Patients: A Pilot Multicenter Randomized Controlled Trial.

(1) Background: In COVID-19 patients, the occurrence of thromboembolic complications contributes to disease progression and mortality. In patients at increased risk for thrombotic complications, therapeutic enoxaparin should be considered. However, critically ill COVID-19 patients could develop resistance to enoxaparin. Bivalirudin, a thrombin inhibitor, may be an alternative. This pilot multicenter randomized controlled trial aims to ascertain if bivalirudin may reduce the time spent under invasive mechanical ventilation, as compared to enoxaparin. (2) Methods: Intubated COVID-19 patients at risk for thrombo-embolic complications were randomized to receive therapeutic doses of enoxaparin or bivalirudin. We ascertained the time spent under invasive mechanical ventilation during the first 28 days from Intensive Care Unit (ICU) admission. A standardized weaning protocol was implemented in all centers. In addition, we assessed the occurrence of thromboembolic complications, the number of patients requiring percutaneous tracheostomy, the gas exchange, the reintubation rate, the ICU length of stay, the ICU and 28-days mortalities. (3) Results: We enrolled 58 consecutive patients. Bivalirudin did not reduce the time spent under invasive mechanical ventilation as compared to enoxaparin (12 [8; 13] vs. 13 [10; 15] days, respectively; p = 0.078). Thrombotic (p = 0.056) and embolic (p = 0.423) complications, need for tracheostomy (p = 0.423) or reintubation (p = 0.999), the ICU length of stay (p = 0.076) and mortality (p = 0.777) were also similar between treatments. Patients randomized to bivalirudin showed a higher oxygenation at day 7 and 15 after randomization, when compared to enoxaparin group. (4) Conclusions: In intubated COVID-19 patients at increased risk for thromboembolic complications, bivalirudin did not reduce the time spent under invasive mechanical ventilation, nor improved any other clinical outcomes.

Should high-flow through nasal cannula be used during bronchoscopy in critically ill patients with hypoxemic acute respiratory failure?

Flexible fiberoptic bronchoscopy (FOB) is an invasive procedure with diagnostic and/or therapeutic purposes commonly used in critically ill patients. FOB may be complicated by desaturation, onset or worsening of the respiratory failure, and hemodynamic instability due to cardio-respiratory alterations occurring during the procedure. Increasing evidences suggest the use of high-flow through nasal cannula (HFNC) over conventional oxygen therapy (COT) in critically ill patients with acute respiratory failure (ARF). Indeed, HFNC has a rationale and possible physiologic advantages, even during FOB. However, to date, evidences in favor of HFNC over COT or continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV) during FOB are still weak. Nonetheless, in critically ill patients with hypoxemic ARF, the choice of the oxygenation strategy during a FOB is challenging. Based on a review of the literature, HFNC may be preferred over COT in patients with mild to moderate hypoxemic ARF, without cardiac failure or hemodynamic instability. On the opposite, in critically ill patients with more severe hypoxemic ARF or in the presence of cardiac failure or hemodynamic instability, CPAP or NIV, applied with specifically designed interfaces, may be preferred over HFNC.

Is the Pendulum of Antimicrobial Drug Resistance Swinging Back after COVID-19?

The COVID-19 pandemic may have had an effect on antimicrobial resistance. We compared the prevalence of ESKAPE multidrug-resistant (MDR) bacterial infections in COVID-19 affected/unaffected patients admitted to intensive care units (ICU) or infectious disease units at the "Mater Domini" University Hospital of Catanzaro between 1 March 2020 and 31 July 2021. Moreover, an analysis of MDR rates in ICU comparing the pre-pandemic period with the pandemic period was performed, and the possible consequence on in-hospital mortality was explored. One hundred and eighty-four ESKAPE isolates were analyzed from 362 SARS-CoV-2 positive and 199 negative patients. In total, 116 out of 171 Gram-negative isolates were classified as MDR, and a higher frequency was observed in COVID-19 compared with non-COVID-19 patients (74.2% vs. 60.3%; p = 0.052). A higher rate of MDR ESKAPE bacteria was observed in COVID-19 patients admitted to the ICU compared with COVID-19 unaffected patients admitted to the same ward in 2019 (88% vs. 80.4%; p = 0.186). Acinetobacter baumannii was the main pathogen in COVID-19 patients (58.7%), where it was the most frequent cause of bloodstream infection with the highest mortality rate (68.7%). Increase in MDR appeared to be associated with COVID-19 but only in the ICU setting. Acinetobacter baumannii was associated with the risk of death, indicating the importance of implementing infection control measures urgently.

Whole-genome analysis of SARS-CoV-2 in a 2020 infection cluster in a nursing home of Southern Italy.

BACKGROUND: Nursing homes have represented important hotspots of viral spread during the initial wave of COVID-19 pandemics. The proximity of patients inside nursing homes allows investigate the dynamics of viral transmission, which may help understand SARS-Cov2 biology and spread. METHODS: SARS-CoV-2 viral genomes obtained from 46 patients infected in an outbreak inside a nursing home in Calabria region (South Italy) were analyzed by Next Generation Sequencing. We also investigated the evolution of viral genomes in 8 patients for which multiple swabs were available. Phylogenetic analysis and haplotype reconstruction were carried out with IQ-TREE software and RegressHaplo tool, respectively. RESULTS: All viral strains isolated from patients infected in the nursing home were classified as B.1 lineage, clade G. Overall, 14 major single nucleotide variations (SNVs) (frequency > 80%) and 12 minor SNVs (frequency comprised between 20% and 80%) were identified with reference to the Wuhan-H-1 sequence (NC_045512.2). All patients presented the same 6 major SNVs: D614G in the S gene; P4715L, ntC3037T (F924F) and S5398P in Orf1ab gene; ntC26681T (F53F) in the M gene; and ntC241T in the non-coding UTR region. However, haplotype reconstruction identified a founder haplotype (Hap A) in 36 patients carrying only the 6 common SNVs indicated above, and 10 other haplotypes (Hap BK) derived from Hap A in the remaining 10 patients. Notably, no significant association between a specific viral haplotype and clinical parameters was found. CONCLUSION: The predominant viral strain responsible for the infection in a nursing home in Calabria was the B.1 lineage (clade G). Viral genomes were classified into 11 haplotypes (Hap A in 36 patients, Hap BK in the remaining patients).

Research on SARS-COV-2 pandemic: a narrative review focused on the Italian contribution.

BACKGROUND: Since late 2019, a severe acute respiratory syndrome, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread with overwhelming speed causing over 214 million confirmed infections and more than 4.5 million deaths worldwide. In this framework, Italy had the second highest number of SARS-CoV-2 infections worldwide, and the largest number of deaths. A global effort of both the scientific community and governments has been undertaken to stem the pandemic. The aim of this paper is to perform a narrative review of the Italian contribution to the scientific literature regarding intensive care management of patients suffering from COVID-19, being one of the first western countries to face an outbreak of SARS-CoV-2 infection. MAIN BODY: We performed a narrative review of the literature, dedicating particular attention and a dedicated paragraph to ventilatory support management, chest imaging findings, biomarkers, possible pharmacological interventions, bacterial superinfections, prognosis and non-clinical key aspects such as communication and interaction with relatives. CONCLUSIONS: Many colleagues, nurses and patients died leaving their families alone. To all of them, we send our thoughts and dedicate these pages.

Vitamin D Serum Levels in Subjects Tested for SARS-CoV-2: What Are the Differences among Acute, Healed, and Negative COVID-19 Patients? A Multicenter Real-Practice Study.

Vitamin D might play a role in counteracting COVID-19, albeit strong evidence is still lacking in the literature. The present multicenter real-practice study aimed to evaluate the differences of 25(OH)D3 serum levels in adults tested for SARS-CoV-2 (acute COVID-19 patients, subjects healed from COVID-19, and non-infected ones) recruited over a 6-month period (March-September 2021). In a sample of 117 subjects, a statistically significant difference was found, with acute COVID-19 patients demonstrating the lowest levels of serum 25(OH)D3 (9.63 ± 8.70 ng/mL), significantly lower than values reported by no-COVID-19 patients (15.96 ± 5.99 ng/mL, p = 0.0091) and healed COVID-19 patients (11.52 ± 4.90 ng/mL, p > 0.05). Male gender across the three groups displayed unfluctuating 25(OH)D3 levels, hinting at an inability to ensure adequate levels of the active vitamin D3 form (1α,25(OH)2D3). As a secondary endpoint, we assessed the correlation between serum 25(OH)D3 levels and pro-inflammatory cytokine interleukin-6 (IL-6) in patients with extremely low serum 25(OH)D3 levels (<1 ng/mL) and in a subset supplemented with 1α,25(OH)2D3. Although patients with severe hypovitaminosis-D showed no significant increase in IL-6 levels, acute COVID-19 patients manifested high circulating IL-6 at admission (females = 127.64 ± 22.24 pg/mL, males = 139.28 ± 48.95 ng/mL) which dropped drastically after the administration of 1α,25(OH)2D3 (1.84 ± 0.77 pg/mL and 2.65 ± 0.92 ng/mL, respectively). Taken together, these findings suggest that an administration of 1α,25(OH)2D3 might be helpful for treating male patients with an acute COVID-19 infection. Further studies on rapid correction of vitamin D deficiency with fast acting metabolites are warranted in COVID-19 patients.

Multidisciplinary approach to a septic COVID-19 patient undergoing veno-venous extracorporeal membrane oxygenation and receiving thoracic surgery.

A multidisciplinary approach appears to be fundamental for the treatment of critically ill patients with COVID-19, improving clinical outcomes, even in the most severe cases. Such severe cases are advisable to be collegially discussed between intensivists, surgeons, infectious disease, and other physicians potentially involved.

Tracheal intubation while wearing personal protective equipment in simulation studies: a systematic review and meta-analysis with trial-sequential analysis.

BACKGROUND: Tracheal intubation in patients with coronavirus disease-19 is a high-risk procedure that should be performed with personal protective equipment (PPE). The influence of PPE on operator's performance during tracheal intubation remains unclear. METHODS: We conducted a systematic review and meta-analysis of simulation studies to evaluate the influence of wearing PPE as compared to standard uniform regarding time-to-intubation (TTI) and success rate. Subgroup analyses were conducted according to device used and operator's experience. RESULTS: The TTI was prolonged when wearing PPE (eight studies): Standard Mean Difference (SMD) -0.54, 95% Confidence Interval [-0.75, -0.34], p <  0.0001. Subgroup analyses according to device used showed similar findings (direct laryngoscopy, SMD -0.63 [-0.88, -0.38], p < 0.0001; videolaryngoscopy, SMD -0.39 [-0.75, -0.02], p =  0.04). Considering the operator's experience, non-anesthesiologists had prolonged TTI (SMD -0.75 [-0.98, -0.52], p < 0.0001) while the analysis on anesthesiologists did not show significant differences (SMD -0.25 [-0.51, 0.01], p = 0.06). The success rate of tracheal intubation was not influenced by PPE: Risk Ratio (RR) 1.02 [1.00, 1.04]; p = 0.12). Subgroup analyses according to device demonstrated similar results (direct laryngoscopy, RR 1.03 [0.99, 1.07], p = 0.15, videolaryngoscopy, RR 1.01 [0.98, 1.04], p =  0.52). Wearing PPE had a trend towards negative influence on success rate in non-anesthesiologists (RR 1.05 [1.00, 1.10], p = 0.05), but not in anesthesiologists (RR 1.00 [0.98, 1.03], p = 0.84). Trial-sequential analyses for TTI and success rate indicated robustness of both results. CONCLUSIONS: Under simulated conditions, wearing PPE delays the TTI as compared to dressing standard uniform, with no influence on the success rate. However, certainty of evidence is very low. Performing tracheal intubation with direct laryngoscopy seems influenced to a greater extent as compared to videolaryngoscopy. Similarly, wearing PPE affects more the non-anesthesiologists subgroup as compared to anesthesiologists.

Early extubation with immediate non-invasive ventilation versus standard weaning in intubated patients for coronavirus disease 2019: a retrospective multicenter study.

In patients intubated for hypoxemic acute respiratory failure (ARF) related to novel coronavirus disease (COVID-19), we retrospectively compared two weaning strategies, early extubation with immediate non-invasive ventilation (NIV) versus standard weaning encompassing spontaneous breathing trial (SBT), with respect to IMV duration (primary endpoint), extubation failures and reintubations, rate of tracheostomy, intensive care unit (ICU) length of stay and mortality (additional endpoints). All COVID-19 adult patients, intubated for hypoxemic ARF and subsequently extubated, were enrolled. Patients were included in two groups, early extubation followed by immediate NIV application, and conventionally weaning after passing SBT. 121 patients were enrolled and analyzed, 66 early extubated and 55 conventionally weaned after passing an SBT. IMV duration was 9 [6-11] days in early extubated patients versus 11 [6-15] days in standard weaning group (p = 0.034). Extubation failures [12 (18.2%) vs. 25 (45.5%), p = 0.002] and reintubations [12 (18.2%) vs. 22 (40.0%) p = 0.009] were fewer in early extubation compared to the standard weaning groups, respectively. Rate of tracheostomy, ICU mortality, and ICU length of stay were no different between groups. Compared to standard weaning, early extubation followed by immediate NIV shortened IMV duration and reduced the rate of extubation failure and reintubation.

Neuron-specific enolase serum levels in COVID-19 are related to the severity of lung injury.

The multifunctional role of neuron-specific enolase (NSE) in lung diseases is well established. As the lungs are greatly affected in COVID-19, we evaluated serum NSE levels in COVID-19 patients with and without dyspnea. In this study, we evaluated both SARS-CoV-2-infected and uninfected patients aged >18 years who were referred to hospitals in Catanzaro, Italy from March 30 to July 30, 2020. Epidemiological, clinical, and radiological characteristics, treatment, and outcome data were recorded and reviewed by a trained team of physicians. In total, 323 patients (178 men, 55.1% and 145 women, 44.9%) were enrolled; of these, 128 were COVID-19 patients (39.6%) and 195 were control patients (60.4%). Westergren's method was used to determine erythroid sedimentation rate. A chemiluminescence assay was used for measurement of interleukin-6, procalcitonin, C-reactive protein, and NSE. We detected significantly higher NSE values (P<0.05) in COVID-19 patients than in controls. Interestingly, within the COVID-19 group, we also observed a further significant increase in dyspnea (Dyspnea Scale and Exercise score: 8.2 ± 0.8; scores ranging from 0 to 10, with higher numbers indicating very severe shortness of breath). These data provide the background for further investigations into the potential role of NSE as a clinical marker of COVID-19 progression.

COVID-19: High-JAKing of the Inflammatory "Flight" by Ruxolitinib to Avoid the Cytokine Storm.

Since SARS-CoV-2 outbreak in December 2019, world health-system has been severely impacted with increased hospitalization, Intensive-Care-Unit (ICU) access and high mortality rates, mostly due to severe acute respiratory failure and multi-organ failure. Excessive and uncontrolled release of proinflammatory cytokines (cytokine release/storm syndrome, CRS) have been linked to the development of these events. The recent advancements of immunotherapy for the treatment of hematologic and solid tumors shed light on many of the molecular mechanisms underlying this phenomenon, thus rendering desirable a multidisciplinary approach to improve COVID-19 patients' outcome. Indeed, currently available therapeutic-strategies to overcome CRS, should be urgently evaluated for their capability of reducing COVID-19 mortality. Notably, COVID-19 shares different pathogenic aspects with acute graft-versus-host-disease (aGVHD), hemophagocytic-lymphohistiocytosis (HLH), myelofibrosis, and CAR-T-associated CRS. Specifically, similarly to aGVHD, an induced tissue damage (caused by the virus) leads to increased cytokine release (TNFα and IL-6) which in turn leads to exaggerated dendritic cells, macrophages (like in HLH) and lymphocytes (as in CAR-T) activation, immune-cells migration, and tissue-damage (including late-stage fibrosis, similar to myelofibrosis). Janus Kinase (JAK) signaling represents a molecular hub linking all these events, rendering JAK-inhibitors suitable to limit deleterious effects of an overwhelming inflammatory-response. Accordingly, ruxolitinib is the only selective JAK1 and JAK2-inhibitor approved for the treatment of myelofibrosis and aGVHD. Here, we discuss, from a molecular and hematological point of view, the rationale for targeting JAK signaling in the management of COVID-19 patients and report the clinical results of a patient admitted to ICU among the firsts to be treated with ruxolitinib in Italy.

Analysis of the persistence time of the SARS-CoV-2 virus in the cadaver and the risk of passing infection to autopsy staff.

The activity of the SARS-CoV-2 virus has not yet been studied in a post-mortem setting. The absence of these data has led to the prohibition of exposure of infected corpses during burial procedures. Our aim was to assess the virus's persistence and the possibility of transmission in the post-mortem phase including autopsy staff. The sample group included 29 patients who were admitted to our Covid-19 Centre who died during hospitalisation and the autopsy staff. All the swabs were subjected to a one-step real-time reverse transcription polymerase chain reaction with cycle threshold (Ct) values. Swab collection was performed at 2 h, 4 h, 6 h, 12 h, over 24 since death. The following were the analysis of patients' swabs: 10 cases were positive 2 h after death; 10 cases positive 4 h after death; 9 cases were found positive 6 h after death; 7 cases positive 12 h after death; 9 cases remained positive 24 h after death. The swabs performed on all the forensic pathologist staff on duty who performed the autopsies were negative. The choice to avoid rituals and the display of corpses before and at the burial procedures given appears cautiously valid due to the persistence of the SARS-CoV-2 virus in the post-mortem period. Although the caution in choosing whether or not to perform an autopsy on infected corpses is acceptable, not to perform autopsies is not biologically supported.

Aggregometry and thromboelastography to identify the timing to trach a COVID-19 patient receiving both antiplatelet therapy and enoxaparin.

In COVID-19 patients receiving enoxaparin and antiplatelets therapy, aggregometry and thromboelastography might be considered an adjunctive tool to identify the time to perform procedures at risk of bleeding, such as tracheostomy.