Impact of SARS-CoV-2 Omicron and Delta variants in patients requiring intensive care unit (ICU) admission for COVID-19, Northern Italy, December 2021 to January 2022.

This multicenter observational study included 171 COVID-19 adult patients hospitalized in the ICUs of nine hospitals in Lombardy (Northern Italy) from December, 1st 2021, to February, 9th 2022. During the study period, the Delta/Omicron variant ratio of cases decreased with a delay of two weeks in ICU patients compared to that in the community; a higher proportion of COVID-19 unvaccinated patients was infected by Delta than by Omicron whereas a higher rate of COVID-19 boosted patients was Omicron-infected. A higher number of comorbidities and a higher comorbidity score in ICU critically COVID-19 inpatients was positively associated with the Omicron infection as well in vaccinated individuals. Although people infected by Omicron have a lower risk of severe disease than those infected by Delta variant, the outcome, including the risk of ICU admission and the need for mechanical ventilation due to infection by Omicron versus Delta, remains uncertain. The continuous monitoring of the circulating SARS-CoV-2 variants remains a milestone to counteract this pandemic.

The Effectiveness of NIV and CPAP Training on the Job in COVID-19 Acute Care Wards: A Nurses' Self-Assessment of Skills.

Background: Noninvasive ventilation (NIV) in COVID-19 patients outside of intensive care unit (ICU) settings was a feasible support during the pandemic outbreak. The aim of this study was to assess the effectiveness of an "on the job" NIV training program provided to 66 nurses working in 3 COVID-19 wards in an Italian university hospital. Methods: A quasi-experimental longitudinal before−after study was designed. The NIV Team education program, provided by expert ICU nurses, included: 3 h sessions of training on the job during work-shifts about the management of helmet-continuous positive airway pressure (CPAP) Venturi systems, and NIV with oronasal and full-face masks. An eleven-item "brief skills self-report tool" was administered before and after the program to explore the perception of NIV education program attendees about their level of skills. Results: In total, 59 nurses responded to the questionnaire. There was an improvement in the skill levels of the management of Helmet-CPAP (median before training 2, inter-quartile range (IQR) 0−6; median after training 8, IQR 3−9; p < 0.0001), and mask-NIV (median before training 2, IQR 0−6; median after training 8, IQR 3−9; p < 0.0001). Conclusions: Training on the job performed by expert ICU nurses can be a valuable and fast means to implement new Helmet-CPAP and mask-NIV skills outside of ICUs.

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.

Recruiting Military Veterans into Alcohol Misuse Research: The Role of Social Media and Facebook Advertising.

Background: The use of digital technology within health care service delivery, monitoring, and research is becoming progressively popular, particularly given the ongoing COVID-19 pandemic. Mobile health (m-health) apps, one form of digital technology, are increasingly being used to promote positive health related behavior change. Therefore, it is important to conduct research to understand the efficacy of m-health apps. The process of participant recruitment is an essential component in producing strong research evidence, along with ensuring an adequately powered sample to conduct meaningful analyses and draw robust conclusions. Methods: In this work we outline and reflect on the strategies used to recruit help-seeking military veterans into an intervention study, which aimed to evaluate the efficacy of an app (Drinks:Ration) to modify behavior in alcohol misusers. Recruitment strategies included through (1) partner organizations and (2) social media and Facebook advertising (ads). Results: Facebook ads were live for a period of 88 days and were viewed by a total audience of 29,416 people. In total 168 military veterans were recruited across all recruitment strategies, meaning that Drinks:Ration exceeded its recruitment targets. Half of the sample (n = 84) were recruited through social media, including Facebook ads. Conclusions: The current article highlighted that targeted Facebook ads were an efficient strategy to recruit military veterans into a digital intervention trial aiming to reduce alcohol consumption because they reduced the amount of time and resources required to contact a large number of potentially eligible individuals for our study. This article acts as a starting point for other researchers to evaluate their recruitment pathways for recruiting military veterans into alcohol misuse research.

Determinants of increased nursing workload in the COVID-era: A retrospective analysis of prospectively collected data.

BACKGROUND: COVID-19 is associated with increased nursing workload, therefore a high nurse-to-patient ratio would be required. AIM: To analyse difference in nursing workload, as expressed with the Nursing Activities Score (NAS), between COVID-19 patients versus control patients without COVID-19 disease (NCOVID-19 group) in an Italian Extracorporeal Membrane Oxygenation (ECMO) centre. STUDY DESIGN: Retrospective analysis of prospectively collected data, enrolling consecutive patients admitted to a general Intensive Care Unit, between 1st May 2019 and 28th February 2021. A multivariate analysis was then performed to assess if COVID-19 disease was an independent predictor of higher NAS and to assess which other factors and procedures are independently associated with increased workload. RESULTS: We enrolled 574 patients, of which 135 (24%) were in the COVID-19 group and 439 (76%) in the NCOVID-19 group. The average NAS was higher in the COVID-19 group (79 ± 11 vs. 65 ± 15, T = -10.026; p < 0.001). Prone positioning, continuous renal replacement therapy (CRRT) and ECMO were used more frequently in the COVID-19 group. A higher fraction of patients in the COVID group showed colonization from multidrug resistant bacteria. COVID-19 group had a higher duration of mechanical ventilation and longer ICU stay. The COVID-19 diagnosis was independently associated with a higher NAS. Other independent predictors of higher NAS were the use of prone positioning and continuous renal replacement therapy (CRRT). Colonization from multidrug resistant bacteria and ECMO support were not independently associated with higher NAS. CONCLUSIONS: The higher nursing workload in COVID-19 patients is mainly due to specific procedures required to treat the most hypoxemic patients, such as prone positioning. Colonization with multidrug resistant bacteria and ECMO support were not independently associated with a higher NAS. RELEVANCE TO CLINICAL PRACTICE: Higher workload in COVID-19 patients was due to specific interventions, such as prone positioning and CRRT, with the related nursing activities, as continuous presence at patient's bed, mobilization, positioning and complex hygienic procedures.

Evaluating the Efficacy of the Drinks:Ration Mobile App to Reduce Alcohol Consumption in a Help-Seeking Military Veteran Population: Randomized Controlled Trial.

BACKGROUND: Alcohol misuse is higher in the UK armed forces (AF) than in the general population. Research demonstrates that alcohol misuse persists after an individual leaves service, and this is notably the case for those who are seeking help for a mental health difficulty. Despite this, there is no work on testing a mobile alcohol reduction intervention that is personalized to support the UK AF. OBJECTIVE: To address this gap, we investigated the efficacy of a 28-day brief alcohol intervention delivered via a mobile app in reducing weekly self-reported alcohol consumption among UK veterans seeking help for mental health difficulties. METHODS: We performed a 2-arm participant-blinded randomized controlled trial (RCT). We compared a mobile app that included interactive features designed to enhance participants' motivation and personalized messaging (intervention arm) with a version that provided government guidance on alcohol consumption only (control arm). Adults were eligible if they had served in the UK AF, were currently receiving or had received clinical support for mental health symptoms, and consumed 14 units (approximately 112 g of ethanol) or more of alcohol per week. Participants received the intervention or the control mobile app (1:1 ratio). The primary outcome was a change in self-reported weekly alcohol consumption between baseline and day 84 assessed using the validated Timeline Follow Back for Alcohol Consumption (TLFB) (prior 7 days), with a secondary outcome exploring self-reported change in the Alcohol Use Disorder Identification Test (AUDIT) score. RESULTS: Between October 2020 and April 2021, 2708 individuals were invited to take part, of which 2531 (93.5%) did not respond, 54 (2%) were ineligible, and 123 (4.5%) responded and were randomly allocated (62, 50.4%, intervention; 61, 49.6%, control). At day 84, 41 (66.1%) participants in the intervention arm and 37 (60.7%) in the control arm completed the primary outcome assessment. Between baseline and day 84, weekly alcohol consumption reduced by -10.5 (95% CI -19.5 to -1.5) units in the control arm and -28.2 (95% CI -36.9 to -19.5) units in the intervention arm (P=.003, Cohen d=0.35). We also found a significant reduction in the AUDIT score of -3.9 (95% CI -6.2 to -1.6) in the intervention arm (Cohen d=0.48). Our primary and secondary effects did not persist over the longer term (day 168). Two adverse events were detected during the trial. CONCLUSIONS: This study examined the efficacy of a fully automated 28-day brief alcohol intervention delivered via a mobile app in a help-seeking sample of UK veterans with hazardous alcohol consumption. We found that participants receiving Drinks:Ration reduced their alcohol consumption more than participants receiving guidance only (at day 84). In the short term, we found Drinks:Ration is efficacious in reducing alcohol consumption in help-seeking veterans. TRIAL REGISTRATION: ClinicalTrials.gov NCT04494594; https://tinyurl.com/34em6n9f. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/19720.

Bedside Selection of Positive End Expiratory Pressure by Electrical Impedance Tomography in Patients Undergoing Veno-Venous Extracorporeal Membrane Oxygenation Support: A Comparison between COVID-19 ARDS and ARDS from Other Etiologies.

BACKGROUND: The interest in protective ventilation strategies and individualized approaches for patients with severe illness on veno venous extracorporeal support has increased in recent years. Wide heterogeneity exists among patients with COVID-19 related acute respiratory distress syndrome (C-ARDS) and ARDS from other etiologies (NC-ARDS). EIT is a useful tool for the accurate analysis of regional lung volume distribution and allows for a tailored ventilatory setting. The aim of this work is to retrospectively describe the results of EIT assessments performed in patients C-ARDS and NC-ARDS undergoing V-V ECMO support. METHODS: A clinical EIT-guided decremental PEEP trail was conducted for all patients included in the study and mechanically ventilated. RESULTS: 12 patients with C-ARDS and 12 patients with NC-ARDS were included in the study for a total of 13 and 18 EIT evaluations, respectively. No significant differences in arterial blood gas, respiratory parameters, and regional ventilation before and after the EIT exam were recorded. The subset of patients with NC-ARDS whose EIT exam led to PEEP modification was characterized by a lower baseline compliance compared with the C-ARDS group: 18 (16-28) vs. 27 (24-30) (p = 0.04). Overdistension significantly increased at higher steps only for the NC-ARDS group. A higher percentage of overdistension was described in patients with NC-ARDS when compared with patients with C-ARDS. CONCLUSIONS: EIT is feasible in patients with COVID-19-associated ARDS on veno-venous extracorporeal support and may help in tailoring the PEEP setting. Overall, severe COVID-19-related ARDS presents respiratory characteristics similar to severe "classical" NC-ARDS. However, C-ARDS is associated with a lower risk of overdistension at a higher PEEP level compared with NC-ARDS.

COVID-19-associated immune-mediated encephalitis mimicking acute-onset Creutzfeldt-Jakob disease.

We report a subtype of immune-mediated encephalitis associated with COVID-19, which closely mimics acute-onset sporadic Creutzfeldt-Jakob disease. A 64-year-old man presented with confusion, aphasia, myoclonus, and a silent interstitial pneumonia. He tested positive for SARS-CoV-2. Cognition and myoclonus rapidly deteriorated, EEG evolved to generalized periodic discharges and brain MRI showed multiple cortical DWI hyperintensities. CSF analysis was normal, except for a positive 14-3-3 protein. RT-QuIC analysis was negative. High levels of pro-inflammatory cytokines were present in the CSF and serum. Treatment with steroids and intravenous immunoglobulins produced EEG and clinical improvement, with a good neurological outcome at a 6-month follow-up.

Short and long-term complications due to standard and extended prone position cycles in CoViD-19 patients.

OBJECTIVE: To investigate short and long-term complications due to standard (≤24 hours) and extended (>24 hours) prone position in COVID-19 patients. METHODS: Retrospective cohort study conducted in an Italian general intensive care unit. We enrolled patients on invasive mechanical ventilation and treated with prone positioning. We recorded short term complications from the data chart and long-term complications from the scheduled follow-up visit, three months after intensive care discharge. RESULTS: A total of 96 patients were included in the study. Median time for each prone positioning cycle (302 cycles) was equal to 18 (16-32) hours. In 37 (38%) patients at least one cycle of extended pronation was implemented. Patients with at least one pressure sore due to prone position were 38 (40%). Patients with pressure sores showed a statistically significative difference in intensive care length of stay, mechanical ventilation days, numbers of prone position cycles, total time spent in prone position and the use of extended prone position, compared to patients without pressure sores. All lesions were low grade. Cheekbones (18%) and chin (10%) were the most affected sites. Follow-up visit, scheduled three months after intensive care discharge, was possible in 58 patients. All patients were able to have all 12 muscle groups examined using theMedical Research Council scale examination. No patient reported sensory loss or presence of neuropathic pain for upper limbs. CONCLUSIONS: Extended prone position is feasible and might reduce the workload on healthcare workers without significant increase of major prone position related complications.

Feasibility of CPAP application and variables related to worsening of respiratory failure in pregnant women with SARS-CoV-2 pneumonia: Experience of a tertiary care centre.

Continuous positive airway pressure (CPAP) has been successfully applied to patients with COVID-19 to prevent endotracheal intubation. However, experience of CPAP application in pregnant women with acute respiratory failure (ARF) due to SARS-CoV-2 pneumonia is scarce. This study aimed to describe the natural history and outcome of ARF in a cohort of pregnant women with SARS-CoV-2 pneumonia, focusing on the feasibility of helmet CPAP (h-CPAP) application and the variables related to ARF worsening. A retrospective, observational study enrolling 41 consecutive pregnant women hospitalised for SARS-CoV-2 pneumonia in a tertiary care center between March 2020 and March 2021. h-CPAP was applied if arterial partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) was inferior to 200 and/or patients had respiratory distress despite adequate oxygen supplementation. Characteristics of patients requiring h-CPAP vs those in room air or oxygen only were compared. Twenty-seven (66%) patients showed hypoxemic ARF requiring oxygen supplementation and h-CPAP was needed in 10 cases (24%). PaO2/FiO2 was significantly improved during h-CPAP application. The device was well-tolerated in all cases with no adverse events. Higher serum C reactive protein and more extensive (≥3 lobes) involvement at chest X-ray upon admission were observed in the h-CPAP group. Assessment of temporal distribution of cases showed a substantially increased rate of CPAP requirement during the third pandemic wave (January-March 2021). In conclusion, h-CPAP was feasible, safe, well-tolerated and improved oxygenation in pregnant women with moderate-to-severe ARF due to SARS-CoV-2 pneumonia. Moderate-to-severe ARF was more frequently observed during the third pandemic wave.

Time course of risk factors associated with mortality of 1260 critically ill patients with COVID-19 admitted to 24 Italian intensive care units.

PURPOSE: To evaluate the daily values and trends over time of relevant clinical, ventilatory and laboratory parameters during the intensive care unit (ICU) stay and their association with outcome in critically ill patients with coronavirus disease 19 (COVID-19). METHODS: In this retrospective-prospective multicentric study, we enrolled COVID-19 patients admitted to Italian ICUs from February 22 to May 31, 2020. Clinical data were daily recorded. The time course of 18 clinical parameters was evaluated by a polynomial maximum likelihood multilevel linear regression model, while a full joint modeling was fit to study the association with ICU outcome. RESULTS: 1260 consecutive critically ill patients with COVID-19 admitted in 24 ICUs were enrolled. 78% were male with a median age of 63 [55-69] years. At ICU admission, the median ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) was 122 [89-175] mmHg. 79% of patients underwent invasive mechanical ventilation. The overall mortality was 34%. Both the daily values and trends of respiratory system compliance, PaO2/FiO2, driving pressure, arterial carbon dioxide partial pressure, creatinine, C-reactive protein, ferritin, neutrophil, neutrophil-lymphocyte ratio, and platelets were associated with survival, while for lactate, pH, bilirubin, lymphocyte, and urea only the daily values were associated with survival. The trends of PaO2/FiO2, respiratory system compliance, driving pressure, creatinine, ferritin, and C-reactive protein showed a higher association with survival compared to the daily values. CONCLUSION: Daily values or trends over time of parameters associated with acute organ dysfunction, acid-base derangement, coagulation impairment, or systemic inflammation were associated with patient survival.

Cytopathology of bronchoalveolar lavages in COVID___19 pneumonia: A pilot study.

BACKGROUND: Bronchoalveolar lavage (BAL) in patients with severe coronavirus disease 2019 (COVID-19) may provide additional and complementary findings for the management of these patients admitted to intensive care units (ICUs). This study addresses the cytological features of the infection and highlights the more influential inflammatory components. The correlation between pathological variables and clinical data is also analyzed. METHODS: The authors performed a retrospective analysis of the cytopathological features of BAL in 20 COVID-19 patients and 20 members of a matched cohort from a critical ICU who had acute respiratory distress syndrome caused by other pulmonary conditions. RESULTS: A comparison of the controls (n = 20) and the COVID-19 patients (n = 20) revealed that the latter had a higher neutrophil count (median, 63.8% of the cell count) with lower percentages of macrophages and lymphocytes. An increase in the expression of CD68-positive, monocytic multinucleated giant cells (MGCs) was reported; megakaryocytes were not detected on CD61 staining. Perls staining showed isolated elements. In situ RNA analysis demonstrated scattered chromogenic signals in type II pneumocytes. An ultrastructural analysis confirmed the presence of intracytoplasmic vacuoles containing rounded structures measuring 140 nm in diameter (putative viral particles). In COVID-19 patients, the clinicopathological correlation revealed a positive correlation between lactate dehydrogenase values and MGCs (r = 0.54). CONCLUSIONS: The analysis of BAL samples might be implemented as a routine practice for the evaluation of COVID-19 patients in ICUs in the appropriate clinical scenario. Additional studies using a larger sample size of patients who developed COVID-19 during the second wave of the epidemic in the autumn of 2020 are needed to further support our findings.

Sigh in Patients With Acute Hypoxemic Respiratory Failure and ARDS: The PROTECTION Pilot Randomized Clinical Trial.

BACKGROUND: Sigh is a cyclic brief recruitment maneuver: previous physiologic studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity, and increase release of surfactant. RESEARCH QUESTION: Is the clinical application of sigh during pressure support ventilation (PSV) feasible? STUDY DESIGN AND METHODS: We conducted a multicenter noninferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or ARDS undergoing PSV. Patients were randomized to the no-sigh group and treated by PSV alone, or to the sigh group, treated by PSV plus sigh (increase in airway pressure to 30 cm H2O for 3 s once per minute) until day 28 or death or successful spontaneous breathing trial. The primary end point of the study was feasibility, assessed as noninferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiologic parameters in the first week from randomization, 28-day mortality, and ventilator-free days. RESULTS: Two-hundred and fifty-eight patients (31% women; median age, 65 [54-75] years) were enrolled. In the sigh group, 23% of patients failed to remain on assisted ventilation vs 30% in the no-sigh group (absolute difference, -7%; 95% CI, -18% to 4%; P = .015 for noninferiority). Adverse events occurred in 12% vs 13% in the sigh vs no-sigh group (P = .852). Oxygenation was improved whereas tidal volume, respiratory rate, and corrected minute ventilation were lower over the first 7 days from randomization in the sigh vs no-sigh group. There was no significant difference in terms of mortality (16% vs 21%; P = .337) and ventilator-free days (22 [7-26] vs 22 [3-25] days; P = .300) for the sigh vs no-sigh group. INTERPRETATION: Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03201263; URL: www.clinicaltrials.gov.

Prone position in intubated, mechanically ventilated patients with COVID-19: a multi-centric study of more than 1000 patients.

BACKGROUND: Limited data are available on the use of prone position in intubated, invasively ventilated patients with Coronavirus disease-19 (COVID-19). Aim of this study is to investigate the use and effect of prone position in this population during the first 2020 pandemic wave. METHODS: Retrospective, multicentre, national cohort study conducted between February 24 and June 14, 2020, in 24 Italian Intensive Care Units (ICU) on adult patients needing invasive mechanical ventilation for respiratory failure caused by COVID-19. Clinical data were collected on the day of ICU admission. Information regarding the use of prone position was collected daily. Follow-up for patient outcomes was performed on July 15, 2020. The respiratory effects of the first prone position were studied in a subset of 78 patients. Patients were classified as Oxygen Responders if the PaO2/FiO2 ratio increased ≥ 20 mmHg during prone position and as Carbon Dioxide Responders if the ventilatory ratio was reduced during prone position. RESULTS: Of 1057 included patients, mild, moderate and severe ARDS was present in 15, 50 and 35% of patients, respectively, and had a resulting mortality of 25, 33 and 41%. Prone position was applied in 61% of the patients. Patients placed prone had a more severe disease and died significantly more (45% vs. 33%, p < 0.001). Overall, prone position induced a significant increase in PaO2/FiO2 ratio, while no change in respiratory system compliance or ventilatory ratio was observed. Seventy-eight % of the subset of 78 patients were Oxygen Responders. Non-Responders had a more severe respiratory failure and died more often in the ICU (65% vs. 38%, p = 0.047). Forty-seven % of patients were defined as Carbon Dioxide Responders. These patients were older and had more comorbidities; however, no difference in terms of ICU mortality was observed (51% vs. 37%, p = 0.189 for Carbon Dioxide Responders and Non-Responders, respectively). CONCLUSIONS: During the COVID-19 pandemic, prone position has been widely adopted to treat mechanically ventilated patients with respiratory failure. The majority of patients improved their oxygenation during prone position, most likely due to a better ventilation perfusion matching. TRIAL REGISTRATION: clinicaltrials.gov number: NCT04388670.

Remdesivir Use in Patients Requiring Mechanical Ventilation due to COVID-19.

BACKGROUND: Remdesivir has been associated with accelerated recovery of severe coronavirus disease 2019 (COVID-19). However, whether it is also beneficial in patients requiring mechanical ventilation is uncertain. METHODS: All consecutive intensive care unit (ICU) patients requiring mechanical ventilation due to COVID-19 were enrolled. Univariate and multivariable Cox models were used to explore the possible association between in-hospital death or hospital discharge, considered competing-risk events, and baseline or treatment-related factors, including the use of remdesivir. The rate of extubation and the number of ventilator-free days were also calculated and compared between treatment groups. RESULTS: One hundred thirteen patients requiring mechanical ventilation were observed for a median of 31 days of follow-up; 32% died, 69% were extubated, and 66% were discharged alive from the hospital. Among 33 treated with remdesivir (RDV), lower mortality (15.2% vs 38.8%) and higher rates of extubation (88% vs 60%), ventilator-free days (median [interquartile range], 11 [0-16] vs 5 [0-14.5]), and hospital discharge (85% vs 59%) were observed. Using multivariable analysis, RDV was significantly associated with hospital discharge (hazard ratio [HR], 2.25; 95% CI, 1.27-3.97; P = .005) and with a nonsignificantly lower mortality (HR, 0.73; 95% CI, 0.26-2.1; P = .560). RDV was also independently associated with extubation (HR, 2.10; 95% CI, 1.19-3.73; P = .011), which was considered a competing risk to death in the ICU in an additional survival model. CONCLUSIONS: In our cohort of mechanically ventilated patients, RDV was not associated with a significant reduction of mortality, but it was consistently associated with shorter duration of mechanical ventilation and higher probability of hospital discharge, independent of other risk factors.