Comparison of Noninvasive Mechanical Ventilation With High-Flow Nasal Cannula, Face-Mask, and Helmet in Hypoxemic Respiratory Failure in Patients With COVID-19: A Randomized Controlled Trial.

OBJECTIVES: For COVID-19-related respiratory failure, noninvasive respiratory assistance via a high-flow nasal cannula (HFNC), helmet, and face-mask noninvasive ventilation is used. However, which of these options is most effective is yet to be determined. This study aimed to compare the three techniques of noninvasive respiratory support and to determine the superior technique. DESIGN: A randomized control trial with permuted block randomization of nine cases per block for each parallel, open-labeled arm. SETTING AND PATIENTS: Adult patients with COVID-19 with a Pao2/Fio2 ratio of less than 300, admitted between February 4, 2021, and August 9, 2021, to three tertiary centers in Oman, were studied. INTERVENTIONS: This study included three interventions: HFNC (n = 47), helmet continuous positive airway pressure (CPAP; n = 52), and face-mask CPAP (n = 52). MEASUREMENTS AND MAIN RESULTS: The endotracheal intubation rate and mortality at 28 and 90 days were measured as the primary and secondary outcomes, respectively. Of the 159 randomized patients, 151 were analyzed. The median age was 52 years, and 74% were men. The endotracheal intubation rates were 44%, 45%, and 46% (p = 0.99), and the median intubation times were 7.0, 5.5, and 4.5 days (p = 0.11) in the HFNC, face-mask CPAP, and helmet CPAP, respectively. In comparison to face-mask CPAP, the relative risk of intubation was 0.97 (95% CI, 0.63-1.49) for HFNC and 1.0 (95% CI 0.66-1.51) for helmet CPAP. The mortality rates were 23%, 32%, and 38% at 28 days (p = 0.24) and 43%, 38%, and 40% (p = 0.89) at 90 days for HFNC, face-mask CPAP, and helmet CPAP, respectively. The trial was stopped prematurely because of a decline in cases. CONCLUSIONS: This exploratory trial found no difference in intubation rate and mortality among the three intervention groups for the COVID-19 patients with hypoxemic respiratory failure; however, more evidence is needed to confirm these findings as the trial was aborted prematurely.

Hospital Memories and Six-Month Psychological Outcome: A Prospective Study in Critical Ill Patients with COVID-19 Respiratory Failure.

ICU survivors suffer from various long-term physical and psychological impairments. Memories from the critical illness may influence long-term psychological outcome. In particular, the role of ICU memories in COVID-19 critically ill patients is unknown. In a prospective observational study, we aimed to investigate patients' memories from the experience of critical illness and their association with a six-month psychological outcome involving quality of life evaluation. Patients' memories were investigated with ICU Memory tool, while psychological outcome and quality of life were evaluated by means of a battery of validated questionnaires during an in-person interview at the follow-up clinic. 149 adult patients were enrolled. 60% retained memories from pre-ICU days spent on a general ward, while 70% reported memories from the in-ICU period. Delusional memories (i.e., memories of facts that never happened) were reported by 69% of patients. According to a multivariable analysis, the lack of pre-ICU memories was an independent predictor of worse psychological outcomes in terms of anxiety, depression and Post-traumatic Stress Disorder (PTDS). Factors associated with long-term outcome in ICU survivors are not still fully understood and patients' experience during the day spent before ICU admission may be associated with psychological sequelae.

Prognostic Performance of Bedside Lung Ultrasound Score (LUSS) and ROX Index in Hypoxemic Respiratory Failure Due to COVID-19.

Background: Noninvasive ventilation, mainly helmet CPAP, was widely used during the COVID-19 pandemic, even outside of intensive care units. Both the ROX index and the LUS score (LUSS) have been proposed as tools to predict negative outcomes in patients with hypoxemia treated with noninvasive ventilation (NIV) outside of ICUs. We aim to evaluate whether the combination of LUSS with the ROX index improves the predictive performance of these indices in patients with hypoxemia due to COVID-19 pneumonia, treated with NIV outside of ICUs. Methods: This is a monocentric prospective observational study conducted at the university teaching hospital Fondazione IRCCS San Gerardo dei Tintori (Monza, Italy) from February to April 2021. LUSS and ROX were collected at the same time in noninvasively ventilated patients outside of the ICU. An LUS exam was performed by 3 emergency medicine attending physicians with at least 5 years' experience in point-of-care ultrasonography using a 12-zone system. To evaluate the accuracy of the prognostic indices in predicting a composite outcome (endotracheal intubation and mortality), ROC curves were used. A logistic multivariable model was used to explore the predictors of the composite outcome of endotracheal intubation and in-hospital mortality. An unadjusted Kaplan-Meier analysis was used to explore the association with the composite outcome of survival without invasive mechanical ventilation at the 30-day follow-up by stratifying the 3 indices by their best cut-offs. Results: A total of 79 patients were included in the statistical analysis and stratified into 2 groups based on the presence of a negative outcome, which was reported in 24 patients out of 79 (30%). A great proportion of patients (66 patients-84%) were treated with helmet CPAP. All three indices (LUSS, ROX and LUSS/ROX) were independently associated with negative outcomes in the multivariable analyses. Although the comparison between the AUROC of LUSS or ROX versus LUSS/ROX did not reveal a statistically significant difference, we observed a trend toward a higher accuracy for predicting negative outcomes using the LUSS/ROX index as compared to using LUSS. With the Kaplan-Maier approach, all three indices stratified by the best cut-off reported a significant association with the outcome of 30-day survival without mechanical ventilation. Conclusions: A multimodal noninvasive approach that combines ultrasound (i.e., LUSS) and a bedside clinical evaluation (i.e., the ROX index) may help clinicians to predict outcomes and to identify patients who would benefit the most from invasive respiratory support.

Inhaled Nitric Oxide in Acute Respiratory Distress Syndrome Subsets: Rationale and Clinical Applications.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition, characterized by diffuse inflammatory lung injury. Since the coronavirus disease 2019 (COVID-19) pandemic spread worldwide, the most common cause of ARDS has been the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Both the COVID-19-associated ARDS and the ARDS related to other causes-also defined as classical ARDS-are burdened by high mortality and morbidity. For these reasons, effective therapeutic interventions are urgently needed. Among them, inhaled nitric oxide (iNO) has been studied in patients with ARDS since 1993 and it is currently under investigation. In this review, we aim at describing the biological and pharmacological rationale of iNO treatment in ARDS by elucidating similarities and differences between classical and COVID-19 ARDS. Thereafter, we present the available evidence on the use of iNO in clinical practice in both types of respiratory failure. Overall, iNO seems a promising agent as it could improve the ventilation/perfusion mismatch, gas exchange impairment, and right ventricular failure, which are reported in ARDS. In addition, iNO may act as a viricidal agent and prevent lung hyperinflammation and thrombosis of the pulmonary vasculature in the specific setting of COVID-19 ARDS. However, the current evidence on the effects of iNO on outcomes is limited and clinical studies are yet to demonstrate any survival benefit by administering iNO in ARDS.

Transfusion practice in patients receiving VV ECMO (PROTECMO): a prospective, multicentre, observational study.

BACKGROUND: In patients receiving venovenous (VV) extracorporeal membrane oxygenation (ECMO) packed red blood cell (PRBC) transfusion thresholds are usually higher than in other patients who are critically ill. Available guidelines suggest a restrictive approach, but do not provide specific recommendations on the topic. The main aim of this study was, in a short timeframe, to describe the actual values of haemoglobin and the rate and the thresholds for transfusion of PRBC during VV ECMO. METHODS: PROTECMO was a multicentre, prospective, cohort study done in 41 ECMO centres in Europe, North America, Asia, and Australia. Consecutive adult patients with acute respiratory distress syndrome (ARDS) who were receiving VV ECMO were eligible for inclusion. Patients younger than 18 years, those who were not able to provide informed consent when required, and patients with an ECMO stay of less than 24 h were excluded. Our main aim was to monitor the daily haemoglobin concentration and the value at the point of PRBC transfusion, as well as the rate of transfusions. The practice in different centres was stratified by continent location and case volume per year. Adjusted estimates were calculated using marginal structural models with inverse probability weighting, accounting for baseline and time varying confounding. FINDINGS: Between Dec 1, 2018, and Feb 22, 2021, 604 patients were enrolled (431 [71%] men, 173 [29%] women; mean age 50 years [SD 13·6]; and mean haemoglobin concentration at cannulation 10·9 g/dL [2·4]). Over 7944 ECMO days, mean haemoglobin concentration was 9·1 g/dL (1·2), with lower concentrations in North America and high-volume centres. PRBC were transfused on 2432 (31%) of days on ECMO, and 504 (83%) patients received at least one PRBC unit. Overall, mean pretransfusion haemoglobin concentration was 8·1 g/dL (1·1), but varied according to the clinical rationale for transfusion. In a time-dependent Cox model, haemoglobin concentration of less than 7 g/dL was consistently associated with higher risk of death in the intensive care unit compared with other higher haemoglobin concentrations (hazard ratio [HR] 2·99 [95% CI 1·95-4·60]); PRBC transfusion was associated with lower risk of death only when transfused when haemoglobin concentration was less than 7 g/dL (HR 0·15 [0·03-0·74]), although no significant effect in reducing mortality was reported for transfusions for other haemoglobin classes (7·0-7·9 g/dL, 8·0-9·9 g/dL, or higher than 10 g/dL). INTERPRETATION: During VV ECMO, there was no universally accepted threshold for transfusion, but PRBC transfusion was invariably associated with lower mortality only when done with haemoglobin concentration of less than 7 g/dL. FUNDING: Extracorporeal Life Support Organization.

Feasibility and preliminary efficacy of brief tele-psychotherapy for COVID-19 patients and their first-degree relatives

Background The SARS-CoV-2 pandemic compromised the mental health of COVID-19 patients and their family members. Due to social distancing and lockdown measures, a remote, tele-psychotherapy program for former or current COVID-19 patients and their relatives was implemented. Objective The primary goal of this project was to evaluate intervention feasibility. The secondary aim was to assess the impact of the intervention by means of pre-post psychological changes. Methods After a phone-based eligibility screening and remote neuropsychological testing, participants completed online self-reports assessing baseline COVID-related psychopathology. Next, participants attended eight tele-psychotherapy sessions. After treatment, the online self-reports were completed again. Results Of 104 enrolled participants, 88 completed the intervention (84.6 % completion rate). Significant pre-post improvements were observed for generalized anxiety (d = 0.38), depression (d = 0.37), insomnia (d = 0.43), post-traumatic psychopathology (d = 0.54), and general malaise (d = 0.31). Baseline cluster analysis revealed a subgroup of 41 subjects (47.6 %) with no psychopathology, and a second subgroup of 45 subject (52.3 %) with moderate severity. Thirty-three percent of the second group reached full symptom remission, while 66 % remained symptomatic after treatment. Conclusions Remote brief tele-psychotherapy for COVID-19 patients and their first-degree relatives is feasible and preliminary efficacious at reducing COVID-related psychopathology in a subgroup of patients. Further research is needed to investigate distinct profiles of treatment response.

Long-term physical impairments in survivors of COVID-19-associated ARDS compared with classic ARDS: A two-center study.

PURPOSE: This work aimed to compare physical impairment in survivors of classic ARDS compared with COVID-19-associated ARDS (CARDS) survivors. MATERIAL AND METHODS: This is a prospective observational cohort study on 248 patients with CARDS and compared them with a historical cohort of 48 patients with classic ARDS. Physical performance was evaluated at 6 and 12 months after ICU discharge, using the Medical Research Council Scale (MRCss), 6-min walk test (6MWT), handgrip dynamometry (HGD), and fatigue severity score (FSS). We also assessed activities of daily living (ADLs) using the Barthel index. RESULTS: At 6 months, patients with classic ARDS had lower HGD (estimated difference [ED]: 11.71 kg, p < 0.001; ED 31.9% of predicted value, p < 0.001), 6MWT distance (ED: 89.11 m, p < 0.001; ED 12.96% of predicted value, p = 0.032), and more frequent significant fatigue (OR 0.35, p = 0.046). At 12 months, patients with classic ARDS had lower HGD (ED: 9.08 kg, p = 0.0014; ED 25.9% of predicted value, p < 0.001) and no difference in terms of 6MWT and fatigue. At 12 months, patients with classic ARDS improved their MRCss (ED 2.50, p = 0.006) and HGD (ED: 4.13 kg, p = 0.002; ED 9.45% of predicted value, p = 0.005), while those with CARDS did not. Most patients in both groups regained independence in ADLs at 6 months. COVID-19 diagnosis was a significant independent predictor of better HGD (p < 0.0001) and 6MWT performance (p = 0.001), and lower prevalence of fatigue (p = 0.018). CONCLUSIONS: Both classic ARDS and CARDS survivors experienced long-term impairments in physical functioning, confirming that post-intensive care syndrome remains a major legacy of critical illness. Surprisingly, however, persisting disability was more common in survivors of classic ARDS than in CARDS survivors. In fact, muscle strength measured with HGD was reduced in survivors of classic ARDS compared to CARDS patients at both 6 and 12 months. The 6MWT was reduced and fatigue was more common in classic ARDS compared to CARDS at 6 months but differences were no longer significant at 12 months. Most patients in both groups regained independent function in ADLs at 6 months.

Feasibility and preliminary efficacy of brief tele-psychotherapy for COVID-19 patients and their first-degree relatives.

BACKGROUND: The SARS-CoV-2 pandemic compromised the mental health of COVID-19 patients and their family members. Due to social distancing and lockdown measures, a remote, tele-psychotherapy program for former or current COVID-19 patients and their relatives was implemented. OBJECTIVE: The primary goal of this project was to evaluate intervention feasibility. The secondary aim was to assess the impact of the intervention by means of pre-post psychological changes. METHODS: After a phone-based eligibility screening and remote neuropsychological testing, participants completed online self-reports assessing baseline COVID-related psychopathology. Next, participants attended eight tele-psychotherapy sessions. After treatment, the online self-reports were completed again. RESULTS: Of 104 enrolled participants, 88 completed the intervention (84.6 % completion rate). Significant pre-post improvements were observed for generalized anxiety (d = 0.38), depression (d = 0.37), insomnia (d = 0.43), post-traumatic psychopathology (d = 0.54), and general malaise (d = 0.31). Baseline cluster analysis revealed a subgroup of 41 subjects (47.6 %) with no psychopathology, and a second subgroup of 45 subject (52.3 %) with moderate severity. Thirty-three percent of the second group reached full symptom remission, while 66 % remained symptomatic after treatment. CONCLUSIONS: Remote brief tele-psychotherapy for COVID-19 patients and their first-degree relatives is feasible and preliminary efficacious at reducing COVID-related psychopathology in a subgroup of patients. Further research is needed to investigate distinct profiles of treatment response.

One hundred ECMO retrivals before and during the Covid-19 pandemic: an observational study.

OBJECTIVES: Patients with severe acute respiratory distress syndrome may require veno-venous extracorporeal membrane oxygenation (V-V ECMO) support. For patients in peripheral hospitals, retrieval by mobile ECMO teams and transport to high-volume centers is associated with improved outcomes, including the recent COVID-19 pandemic. To enable a safe transport of patients, a specialised ECMO-retrieval program needs to be implemented. However, there is insufficient evidence on how to safely and efficiently perform ECMO retrievals. We report single-centre data from out-of-centre initiations of VV-ECMO before and during the COVID-19 pandemic. DESIGN & SETTING: Single-centre retrospective study. We include all the retrievals performed by our ECMO centre between January 1st, 2014, and April 30th, 2021. RESULTS: One hundred ECMO missions were performed in the study period, for a median retrieval volume of 13 (IQR: 9-16) missions per year. the cause of the acute respiratory distress syndrome was COVID-19 in 10 patients (10 %). 98 (98 %) patients were retrieved and transported to our ECMO centre. To allow safe transport, 91 of them were cannulated on-site and transported on V-V ECMO. The remaining seven patients were centralised without ECMO, but they were all connected to V-V ECMO in the first 24 hours. No complications occurred during patient transport. The median duration of the ECMO mission was 7 hours (IQR: 6-9, range: 2 - 17). Median duration of ECMO support was 14 days (IQR: 9-24), whereas the ICU stay was 24 days (IQR:18-44). Overall, 73 patients were alive at hospital discharge (74 %). Survival rate was similar in non-COVID-19 and COVID-19 group (73 % vs 80 %, p = 0.549). CONCLUSION: In this single-centre experience, before and during COVID-19 era, retrieval and ground transportation of ECMO patients was feasible and was not associated with complications. Key factors of an ECMO retrieval program include a careful selection of the transport ambulance, training of a dedicated ECMO mobile team and preparation of specific checklists and standard operating procedures.

Tracheal stenting on venovenous ECMO with a dual lumen right atrium-to-pulmonary artery cannula in a COVID-19 patient with an inferior vena cava filter.

A 47-year-old man, with no medical history, was diagnosed with severe COVID-19 ARDS and pulmonary embolism. Venovenous extracorporeal membrane oxygenation (ECMO) was required for impossibility to deliver protective ventilation. The patient was weaned from ECMO after clinical improvement. An inferior vena cava filter was then positioned to prevent embolization from a persistent left femoral deep venous thrombosis. Two days after the ECMO removal, a large lesion of the tracheal posterior wall was diagnosed. Tracheal stenting was deemed necessary. ECMO support was then re-established, to safely perform the bronchoscopic procedure. Due to the presence of the inferior vena cava filter, the patient was cannulated via the right internal jugular vein with a double lumen ProtekDuo cannula. The patient was then weaned from ECMO support and invasive ventilation. The tracheal stent was removed after 40 days, showing a full recovery of the tracheal lesion. The patient was discharged home in good condition.

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.

Frailty and long-COVID: is COVID-19 responsible for a transition in frailty status among older adults who survived hospitalization for COVID-19?

BACKGROUND: There is a paucity of knowledge about the effects of COronaVIrus Disease-19 (COVID-19) on long-term frailty development or progression over time. AIM: This study aims to assess transitions in frailty status in older adults who survived hospitalization for COVID-19. METHODS: This is a longitudinal panel study. A multidisciplinary outpatient follow-up service was established since summer 2020, for the evaluation of individuals discharged alive, after hospitalization due to COVID-19. Frailty status was assessed in-hospital and at follow-up using the clinical frailty scale (CFS). Main patients' characteristics, including health, functional, cognitive, and psychological status were collected. RESULTS: A total of 177 patients aged 65 years and older were evaluated until June 2022. They were predominantly male, with a median age of 70 (Q1-Q3 67-75) years and a median body mass index of 27.5 (Q1-Q3 24.9-30.6) kg/m2 at hospital admission. The median follow-up time was 6.3 (Q1-Q3 3.7-10.9) months. Sixty-one patients (34.5%) scored worse at CFS follow-up compared to hospital admission, and twenty-two patients (12.4%) became frail. DISCUSSION AND CONCLUSION: This study shows that one out of three older patients previously hospitalized for COVID-19 had an unfavorable transition in CFS score during a median follow-up of nearly 6 months. Specific interventions to prevent frailty development or progression should be considered for patients at risk. Further studies are required to confirm our findings.

The PROVENT-C19 registry: A study protocol for international multicenter SIAARTI registry on the use of prone positioning in mechanically ventilated patients with COVID-19 ARDS.

BACKGROUND: The worldwide use of prone position (PP) for invasively ventilated patients with COVID-19 is progressively increasing from the first pandemic wave in everyday clinical practice. Among the suggested treatments for the management of ARDS patients, PP was recommended in the Surviving Sepsis Campaign COVID-19 guidelines as an adjuvant therapy for improving ventilation. In patients with severe classical ARDS, some authors reported that early application of prolonged PP sessions significantly decreases 28-day and 90-day mortality. METHODS AND ANALYSIS: Since January 2021, the COVID19 Veneto ICU Network research group has developed and implemented nationally and internationally the "PROVENT-C19 Registry", endorsed by the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care…'(SIAARTI). The PROVENT-C19 Registry wishes to describe 1. The real clinical practice on the use of PP in COVID-19 patients during the pandemic at a National and International level; and 2. Potential baseline and clinical characteristics that identify subpopulations of invasively ventilated patients with COVID-19 that may improve daily from PP therapy. This web-based registry will provide relevant information on how the database research tools may improve our daily clinical practice. CONCLUSIONS: This multicenter, prospective registry is the first to identify and characterize the role of PP on clinical outcome in COVID-19 patients. In recent years, data emerging from large registries have been increasingly used to provide real-world evidence on the effectiveness, quality, and safety of a clinical intervention. Indeed observation-based registries could be effective tools aimed at identifying specific clusters of patients within a large study population with widely heterogeneous clinical characteristics. TRIAL REGISTRATION: The registry was registered (ClinicalTrial.Gov Trials Register NCT04905875) on May 28,2021.

Femorally inserted central catheters with exit site at mid-thigh: A low risk alternative for central venous catheterization.

BACKGROUND: Femorally inserted central catheters are increasingly used, especially after the COVID-19 pandemic, also thanks to widespread of tunneling techniques that allow the exit site to be moved away from the groin. METHODS: In this retrospective observational study, femorally inserted catheters, with exit site at mid-thigh and the tip in Inferior vena cava or in Inferior vena cava at the junction with right atrium, have been observed and complications have been analyzed. All catheters were inserted by trained Nurses of a tertiary hospital Vascular Access Team. RESULTS: In 142 catheters (126 inserted via common femoral vein and 16 inserted via superficial femoral vein) and 3060 catheter days, we observed an infection rate of 1.3 events/1000 catheter days (all of them in oncologic patients and up to 30 days of catheterization), 2 cases of thrombotic events (1.41%) and 17 cases of accidental removal (11.97%). Other rare complications, as primary malposition, tip migration, arterial pseudoaneurysm, have been recorded. The average length of catheters inserted, from the exit site to the tip, was 47.6 ± 2.4 cm. CONCLUSION: The attention to the correct position of the tip, the exit site at mid-thigh and the new techniques during insertion make these femoral catheters as safe as other central vascular access devices. For this kind of central access device, a catheter at least 50 cm long is needed.

Association of COVID-19 Vaccinations With Intensive Care Unit Admissions and Outcome of Critically Ill Patients With COVID-19 Pneumonia in Lombardy, Italy.

Importance: Data on the association of COVID-19 vaccination with intensive care unit (ICU) admission and outcomes of patients with SARS-CoV-2-related pneumonia are scarce. Objective: To evaluate whether COVID-19 vaccination is associated with preventing ICU admission for COVID-19 pneumonia and to compare baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU. Design, Setting, and Participants: This retrospective cohort study on regional data sets reports: (1) daily number of administered vaccines and (2) data of all consecutive patients admitted to an ICU in Lombardy, Italy, from August 1 to December 15, 2021 (Delta variant predominant). Vaccinated patients received either mRNA vaccines (BNT162b2 or mRNA-1273) or adenoviral vector vaccines (ChAdOx1-S or Ad26.COV2). Incident rate ratios (IRRs) were computed from August 1, 2021, to January 31, 2022; ICU and baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU were analyzed from August 1 to December 15, 2021. Exposures: COVID-19 vaccination status (no vaccination, mRNA vaccine, adenoviral vector vaccine). Main Outcomes and Measures: The incidence IRR of ICU admission was evaluated, comparing vaccinated people with unvaccinated, adjusted for age and sex. The baseline characteristics at ICU admission of vaccinated and unvaccinated patients were investigated. The association between vaccination status at ICU admission and mortality at ICU and hospital discharge were also studied, adjusting for possible confounders. Results: Among the 10 107 674 inhabitants of Lombardy, Italy, at the time of this study, the median [IQR] age was 48 [28-64] years and 5 154 914 (51.0%) were female. Of the 7 863 417 individuals who were vaccinated (median [IQR] age: 53 [33-68] years; 4 010 343 [51.4%] female), 6 251 417 (79.5%) received an mRNA vaccine, 550 439 (7.0%) received an adenoviral vector vaccine, and 1 061 561 (13.5%) received a mix of vaccines and 4 497 875 (57.2%) were boosted. Compared with unvaccinated people, IRR of individuals who received an mRNA vaccine within 120 days from the last dose was 0.03 (95% CI, 0.03-0.04; P < .001), whereas IRR of individuals who received an adenoviral vector vaccine after 120 days was 0.21 (95% CI, 0.19-0.24; P < .001). There were 553 patients admitted to an ICU for COVID-19 pneumonia during the study period: 139 patients (25.1%) were vaccinated and 414 (74.9%) were unvaccinated. Compared with unvaccinated patients, vaccinated patients were older (median [IQR]: 72 [66-76] vs 60 [51-69] years; P < .001), primarily male individuals (110 patients [79.1%] vs 252 patients [60.9%]; P < .001), with more comorbidities (median [IQR]: 2 [1-3] vs 0 [0-1] comorbidities; P < .001) and had higher ratio of arterial partial pressure of oxygen (Pao2) and fraction of inspiratory oxygen (FiO2) at ICU admission (median [IQR]: 138 [100-180] vs 120 [90-158] mm Hg; P = .007). Factors associated with ICU and hospital mortality were higher age, premorbid heart disease, lower Pao2/FiO2 at ICU admission, and female sex (this factor only for ICU mortality). ICU and hospital mortality were similar between vaccinated and unvaccinated patients. Conclusions and Relevance: In this cohort study, mRNA and adenoviral vector vaccines were associated with significantly lower risk of ICU admission for COVID-19 pneumonia. ICU and hospital mortality were not associated with vaccinated status. These findings suggest a substantial reduction of the risk of developing COVID-19-related severe acute respiratory failure requiring ICU admission among vaccinated people.

Neurological Manifestations of SARS-CoV-2 Infection: Protocol for a Sub-analysis of the COVID-19 Critical Care Consortium Observational Study.

Introduction: Neurological manifestations and complications in coronavirus disease-2019 (COVID-19) patients are frequent. Prior studies suggested a possible association between neurological complications and fatal outcome, as well as the existence of potential modifiable risk factors associated to their occurrence. Therefore, more information is needed regarding the incidence and type of neurological complications, risk factors, and associated outcomes in COVID-19. Methods: This is a pre-planned secondary analysis of the international multicenter observational study of the COVID-19 Critical Care Consortium (which collected data both retrospectively and prospectively from the beginning of COVID-19 pandemic) with the aim to describe neurological complications in critically ill COVID-19 patients and to assess the associated risk factors, and outcomes. Adult patients with confirmed COVID-19, admitted to Intensive Care Unit (ICU) will be considered for this analysis. Data collected in the COVID-19 Critical Care Consortium study includes patients' pre-admission characteristics, comorbidities, severity status, and type and severity of neurological complications. In-hospital mortality and neurological outcome were collected at discharge from ICU, and at 28-days. Ethics and Dissemination: The COVID-19 Critical Care Consortium main study and its amendments have been approved by the Regional Ethics Committee of participating sites. No further approval is required for this secondary analysis. Trial Registration Number: ACTRN12620000421932.

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.

Intravenous methylprednisolone pulses in hospitalised patients with severe COVID-19 pneumonia: a double-blind, randomised, placebo-controlled trial.

RATIONALE: Pulse glucocorticoid therapy is used in hyperinflammation related to coronavirus disease 2019 (COVID-19). We evaluated the efficacy and safety of pulse intravenous methylprednisolone in addition to standard treatment in COVID-19 pneumonia. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, 304 hospitalised patients with COVID-19 pneumonia were randomised to receive 1 g of methylprednisolone intravenously for three consecutive days or placebo in addition to standard dexamethasone. The primary outcome was the duration of patient hospitalisation, calculated as the time interval between randomisation and hospital discharge without the need for supplementary oxygen. The key secondary outcomes were survival free from invasive ventilation with orotracheal intubation and overall survival. RESULTS: Overall, 112 (75.4%) out of 151 patients in the pulse methylprednisolone arm and 111 (75.2%) of 150 in the placebo arm were discharged from hospital without oxygen within 30 days from randomisation. Median time to discharge was similar in both groups (15 days, 95% CI 13.0-17.0 days and 16 days, 95% CI 13.8-18.2 days, respectively; hazard ratio (HR) 0.92, 95% CI 0.71-1.20; p=0.528). No significant differences between pulse methylprednisolone and placebo arms were observed in terms of admission to intensive care unit with orotracheal intubation or death (20.0% versus 16.1%; HR 1.26, 95% CI 0.74-2.16; p=0.176) or overall mortality (10.0% versus 12.2%; HR 0.83, 95% CI 0.42-1.64; p=0.584). Serious adverse events occurred with similar frequency in the two groups. CONCLUSIONS: Methylprenisolone pulse therapy added to dexamethasone was not of benefit in patients with COVID-19 pneumonia.