Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19.

BACKGROUND: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. METHODS: The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). RESULTS: Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. CONCLUSIONS: Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death.

In-hospital and 6-month outcomes in patients with COVID-19 supported with extracorporeal membrane oxygenation (EuroECMO-COVID): a multicentre, prospective observational study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with COVID-19, but uncertainty remains about the determinants of in-hospital mortality and data on post-discharge outcomes are scarce. The aims of this study were to investigate the variables associated with in-hospital outcomes in patients who received ECMO during the first wave of COVID-19 and to describe the status of patients 6 months after ECMO initiation. METHODS: EuroECMO-COVID is a prospective, multicentre, observational study developed by the European Extracorporeal Life Support Organization. This study was based on data from patients aged 16 years or older who received ECMO support for refractory COVID-19 during the first wave of the pandemic-from March 1 to Sept 13, 2020-at 133 centres in 21 countries. In-hospital mortality and mortality 6 months after ECMO initiation were the primary outcomes. Mixed-Cox proportional hazards models were used to investigate associations between patient and management-related variables (eg, patient demographics, comorbidities, pre-ECMO status, and ECMO characteristics and complications) and in-hospital deaths. Survival status at 6 months was established through patient contact or institutional charts review. This study is registered with ClinicalTrials.gov, NCT04366921, and is ongoing. FINDINGS: Between March 1 and Sept 13, 2020, 1215 patients (942 [78%] men and 267 [22%] women; median age 53 years [IQR 46-60]) were included in the study. Median ECMO duration was 15 days (IQR 8-27). 602 (50%) of 1215 patients died in hospital, and 852 (74%) patients had at least one complication. Multiorgan failure was the leading cause of death (192 [36%] of 528 patients who died with available data). In mixed-Cox analyses, age of 60 years or older, use of inotropes and vasopressors before ECMO initiation, chronic renal failure, and time from intubation to ECMO initiation of 4 days or more were associated with higher in-hospital mortality. 613 patients did not die in hospital, and 547 (95%) of 577 patients for whom data were available were alive at 6 months. 102 (24%) of 431 patients had returned to full-time work at 6 months, and 57 (13%) of 428 patients had returned to part-time work. At 6 months, respiratory rehabilitation was required in 88 (17%) of 522 patients with available data, and the most common residual symptoms included dyspnoea (185 [35%] of 523 patients) and cardiac (52 [10%] of 514 patients) or neurocognitive (66 [13%] of 512 patients) symptoms. INTERPRETATION: Patient's age, timing of cannulation (<4 days vs ≥4 days from intubation), and use of inotropes and vasopressors are essential factors to consider when analysing the outcomes of patients receiving ECMO for COVID-19. Despite post-discharge survival being favourable, persisting long-term symptoms suggest that dedicated post-ECMO follow-up programmes are required. FUNDING: None.

The Use of Noninvasive Multimodal Neuromonitoring in Adult Critically Ill Patients With COVID-19 Infection.

INTRODUCTION: Noninvasive neuromonitoring could be a valuable option for bedside assessment of cerebral dysfunction in patients with coronavirus disease-2019 (COVID-19) admitted to intensive care units (ICUs). This systematic review aims to investigate the use of noninvasive multimodal neuromonitoring in critically ill adult patients with COVID-19 infection. METHODS: MEDLINE/PubMed, Scopus, Cochrane, and EMBASE databases were searched for studies investigating noninvasive neuromonitoring in patients with COVID-19 admitted to ICUs. The monitoring included transcranial Doppler ultrasonography (TCD), the Brain4care Corp. cerebral compliance monitor (B4C), optic nerve sheath diameter (ONSD), near infrared spectroscopy, automated pupillometry, and electroencephalography (EEG). RESULTS: Thirty-two studies that investigated noninvasive neuromonitoring techniques in patients with COVID-19 in the ICU were identified from a systematic search of 7001 articles: 1 study investigating TCD, ONSD and pupillometry; 2 studies investigating the B4C device and TCD; 3 studies investigating near infrared spectroscopy and TCD; 4 studies investigating TCD; 1 case series investigating pupillometry, and 21 studies investigating EEG. One hundred and nineteen patients underwent TCD monitoring, 47 pupillometry, 49 ONSD assessment, 50 compliance monitoring with the B4C device, and 900 EEG monitoring. Alterations in cerebral hemodynamics, brain compliance, brain oxygenation, pupillary response, and brain electrophysiological activity were common in patients with COVID-19 admitted to the ICU; these abnormalities were not clearly associated with worse outcome or the development of new neurological complications. CONCLUSIONS: The use of noninvasive multimodal neuromonitoring in critically ill COVID-19 patients could be considered to facilitate the detection of neurological derangements. Determining whether such findings allow earlier detection of neurological complications or guide appropriate therapy requires additional studies.

Early Prediction of High-Flow Oxygen Therapy Failure in COVID-19 Acute Hypoxemic Respiratory Failure: A Retrospective Study of Scores and Thresholds.

Background High-flow oxygen therapy (HFOT) has been widely used as an effective alternative to invasive mechanical ventilation (IMV) in some critically ill patients with COVID-19 pneumonia. This study aimed to compare different tools, including the respiratory rate and oxygenation (ROX) index, to predict HFOT failure in this setting. Methodology This single-center retrospective observational study was conducted from September to December 2020 and assessed COVID-19 patients who required HFOT as the first treatment at admission; HFOT failure was defined as IMV use. Prognostic scoring tools were as follows: the Sequential Organ Failure Assessment (SOFA), Acute Physiology And Chronic Health Evaluation (APACHE) II, and Simplified Acute Physiology Score (SAPS) III scores; C-reactive protein; lung consolidation percentage on chest CT; mean partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FiO2) ratio; and ROX index and modified ROX index, calculated using PaO2 instead of blood oxygen saturation, within the first 24 hours after admission to the intensive care unit (ICU). These scores were analyzed using a multivariate Cox proportional hazard model; optimal cutoffs were computed using the R system for statistical computing. Results The study enrolled 52 patients, 31 (60%) of whom experienced HFOT failure. The best predictors of HFOT failure measured 24 hours after HFOT initiation were as follows: PaO2/FiO2 (threshold 123.6, sensitivity 87%, specificity 81%, hazard ratio [HR] 7.76, and 95% confidence interval [CI] 2.39-17.1); ROX index (threshold 5.63, sensitivity 68%, specificity 95%, HR 6.18, and 95% CI 2.54-13.4); and modified ROX index (threshold 4.94, sensitivity 81%, specificity 90%, HR 8.16, and 95% CI 3.16-21.5) (P < 0.001 for all). Conclusions Early assessment of the ROX index, modified ROX index, and PaO2/FiO2 ratio can adequately predict, with high accuracy, HFOT failure in COVID-19 patients. Because thresholds remain debated and are still not sufficiently validated, we advocate using them with caution for clinical decision-making in this context.

Early procalcitonin to predict mortality in critically ill COVID-19 patients: a multicentric cohort study.

BACKGROUND: High levels of procalcitonin (PCT) have been associated with a higher risk of mortality in COVID-19 patients. We explored the prognostic role of early PCT assessment in critically ill COVID-19 patients and whether PCT predictive performance would be influenced by immunosuppression. METHODS: Retrospective multicentric analysis of prospective collected data in COVID-19 patients consecutively admitted to 36 intensive care units (ICUs) in Spain and Andorra from March to June 2020. Adult (>18 years) patients with confirmed COVID-19 and available PCT values (<72 hours from ICU admission) were included. Patients were considered as "no immunosuppression" (NI), "chronic immunosuppression" (CI) and "acute immunosuppression" (AIT if only tocilizumab; AIS if only steroids, AITS if both). The primary outcome was the ability of PCT to predict ICU mortality. RESULTS: Of the 1079 eligible patients, 777 patients were included in the analysis. Mortality occurred in 227 (28%) patients. In the NI group 144 (19%) patients were included, 67 (9%) in the CI group, 66 (8%) in the AIT group, 262 (34%) in the AIS group and 238 (31%) in the AITS group; PCT was significantly higher in non-survivors when compared with survivors (0.64 [0.17-1.44] vs. 0.23 [0.11-0.60] ng/mL; P<0.01); however, in the multivariable analysis, PCT values was not independently associated with ICU mortality. PCT values and ICU mortality were significantly higher in patients in the NI and CI groups. CONCLUSIONS: PCT values are not independent predictors of ICU mortality in COVID-19 patients. Acute immunosuppression significantly reduced PCT values, although not influencing its predictive value.

Outcomes of Extracorporeal Membrane Oxygenation in COVID-19–Induced Acute Respiratory Distress Syndrome: An Inverse Probability Weighted Analysis

IMPORTANCE: Although venovenous extracorporeal membrane oxygenation (VV ECMO) has been used in case of COVID-19 induced acute respiratory distress syndrome (ARDS), outcomes and criteria for its application should be evaluated. OBJECTIVES: To describe patient characteristics and outcomes in patients receiving VV ECMO due to COVID-19–induced ARDS and to assess the possible impact of COVID-19 on mortality. DESIGN, SETTING AND PARTICIPANTS: Multicenter retrospective study in 15 ICUs worldwide. All adult patients (> 18 yr) were included if they received VV ECMO with ARDS as main indication. Two groups were created: a COVID-19 cohort from March 2020 to December 2020 and a “control” non-COVID ARDS cohort from January 2018 to July 2019. MAIN OUTCOMES AND MEASURES: Collected data consisted of patient demographics, baseline variables, ECMO characteristics, and patient outcomes. The primary outcome was 60-day mortality. Secondary outcomes included patient characteristics, COVID-19–related therapies before and during ECMO and complication rate. To assess the influence of COVID-19 on mortality, inverse probability weighted (IPW) analyses were used to correct for predefined confounding variables. RESULTS: A total of 193 patients with COVID-19 received VV ECMO. The main indication for VV ECMO consisted of refractory hypoxemia, either isolated or combined with refractory hypercapnia. Complications with the highest occurrence rate included hemorrhage, an additional infectious event or acute kidney injury. Mortality was 35% and 45% at 28 and 60 days, respectively. Those mortality rates did not differ between the first and second waves of COVID-19 in 2020. Furthermore, 60-day mortality was equal between patients with COVID-19 and non-COVID-19–associated ARDS receiving VV ECMO (hazard ratio 60-d mortality, 1.27;95% CI, 0.82–1.98;p = 0.30). CONCLUSIONS AND RELEVANCE: Mortality for patients with COVID-19 who received VV ECMO was similar to that reported in other COVID-19 cohorts, although no differences were found between the first and second waves regarding mortality. In addition, after IPW, mortality was independent of the etiology of ARDS.

Veno-venous extra-corporeal membrane oxygenation in a COVID-19 patient with cold-agglutinin haemolytic anaemia: A case report.

OVERVIEW: The use of extra-corporeal membrane oxygenation (ECMO) therapy to treat severe COVID-19 patients with acute respiratory failure is increasing worldwide. We reported herein the use of veno-venous ECMO in a patient with cold agglutinin haemolytic anaemia (CAHA) who suffered from severe COVID-19 infection. DESCRIPTION: A 64-year-old man presented to the emergency department (ED) with incremental complaints of dyspnoea and cough since one week. His history consisted of CAHA, which responded well to corticosteroid treatment. Because of severe hypoxemia, urgent intubation and mechanical ventilation were necessary. Despite deep sedation, muscle paralysis and prone ventilation, P/F ratio remained low. Though his history of CAHA, he still was considered for VV-ECMO. As lab results pointed to recurrence of CAHA, corticosteroids and rituximab were started. The VV-ECMO run was short and rather uncomplicated. Although, despite treatment, CAHA persisted and caused important complications of intestinal ischemia, which needed multiple surgical interventions. Finally, the patient suffered from progressive liver failure, thought to be secondary to ischemic cholangitis. One month after admission, therapy was stopped and patient passed away. CONCLUSION: Our case report shows that CAHA is no contraindication for VV-ECMO, even when both titre and thermal amplitude are high. Although, the aetiology of CAHA and its response to therapy will determine the final outcome of those patients.

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study.

BACKGROUND: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). METHODS: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. RESULTS: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). CONCLUSIONS: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.

A Retrospective, Monocentric Study Comparing Co and Secondary Infections in Critically Ill COVID-19 and Influenza Patients.

Few data are available on infectious complications in critically ill patients with different viral infections. We performed a retrospective monocentric study including all of the patients admitted to the intensive care unit (ICU) with confirmed COVID-19 (as of 13 March 2020) or Influenza A and/or B infections (as of 1 January 2015) until 20 April 2020. Coinfection and secondary infections (occurring within and after 48 h from admission, respectively) were recorded. Fifty-seven COVID-19 and 55 Influenza patients were included. Co-infections were documented in 13/57 (23%) COVID-19 patients vs. 40/55 (73%) Influenza patients (p < 0.001), most of them being respiratory (9/13, 69% vs. 35/40, 88%; p = 0.13) and of bacterial origin (12/13, 92% vs. 29/40, 73%; p = 0.25). Invasive aspergillosis infections were observed only in Influenza patients (8/55, 15%). The COVID-19 and Influenza patients presented 1 (0-4) vs. 0 (0-4) secondary infections (p = 0.022), with comparable sites being affected (lungs: 35/61, 57% vs. 13/31, 42%; p = 0.16) and causative pathogens occurring (Gram-negative bacteria: 51/61, 84% vs. 23/31, 74%; p > 0.99). The COVID-19 patients had longer ICU lengths of stay (15 (-65) vs. 5 (1-89) days; p = 0.001), yet the two groups had comparable mortality rates (20/57, 35% vs. 23/55, 41%; p = 0.46). We report fewer co-infections but more secondary infections in the ICU COVID-19 patients compared to the Influenza patients. Most of the infectious complications were respiratory and of bacterial origin.

A Retrospective, Monocentric Study Comparing Co and Secondary Infections in Critically Ill COVID-19 and Influenza Patients

Few data are available on infectious complications in critically ill patients with different viral infections. We performed a retrospective monocentric study including all of the patients admitted to the intensive care unit (ICU) with confirmed COVID-19 (as of 13 March 2020) or Influenza A and/or B infections (as of 1 January 2015) until 20 April 2020. Coinfection and secondary infections (occurring within and after 48 h from admission, respectively) were recorded. Fifty-seven COVID-19 and 55 Influenza patients were included. Co-infections were documented in 13/57 (23%) COVID-19 patients vs. 40/55 (73%) Influenza patients (p < 0.001), most of them being respiratory (9/13, 69% vs. 35/40, 88%;p = 0.13) and of bacterial origin (12/13, 92% vs. 29/40, 73%;p = 0.25). Invasive aspergillosis infections were observed only in Influenza patients (8/55, 15%). The COVID-19 and Influenza patients presented 1 (0–4) vs. 0 (0–4) secondary infections (p = 0.022), with comparable sites being affected (lungs: 35/61, 57% vs. 13/31, 42%;p = 0.16) and causative pathogens occurring (Gram-negative bacteria: 51/61, 84% vs. 23/31, 74%;p > 0.99). The COVID-19 patients had longer ICU lengths of stay (15 (–65) vs. 5 (1–89) days;p = 0.001), yet the two groups had comparable mortality rates (20/57, 35% vs. 23/55, 41%;p = 0.46). We report fewer co-infections but more secondary infections in the ICU COVID-19 patients compared to the Influenza patients. Most of the infectious complications were respiratory and of bacterial origin.

Non-Invasive Multimodal Neuromonitoring in Non-Critically Ill Hospitalized Adult Patients With COVID-19: A Systematic Review and Meta-Analysis.

Introduction: Neurological complications are frequent in patients with coronavirus disease-2019 (COVID-19). The use of non-invasive neuromonitoring in subjects without primary brain injury but with potential neurological derangement is gaining attention outside the intensive care unit (ICU). This systematic review and meta-analysis investigates the use of non-invasive multimodal neuromonitoring of the brain in non-critically ill patients with COVID-19 outside the ICU and quantifies the prevalence of abnormal neuromonitoring findings in this population. Methods: A structured literature search was performed in MEDLINE/PubMed, Scopus, Cochrane, and EMBASE to investigate the use of non-invasive neuromonitoring tools, including transcranial doppler (TCD); optic nerve sheath diameter (ONSD); near-infrared spectroscopy (NIRS); pupillometry; and electroencephalography (EEG) inpatients with COVID-19 outside the ICU. The proportion of non-ICU patients with CVOID-19 and a particular neurological feature at neuromonitoring at the study time was defined as prevalence. Results: A total of 6,593 records were identified through literature searching. Twenty-one studies were finally selected, comprising 368 non-ICU patients, of whom 97 were considered for the prevalence of meta-analysis. The pooled prevalence of electroencephalographic seizures, periodic and rhythmic patterns, slow background abnormalities, and abnormal background on EEG was.17 (95% CI 0.04-0.29), 0.42 (95% CI 0.01-0.82), 0.92 (95% CI 0.83-1.01), and.95 (95% CI 0.088-1.09), respectively. No studies investigating NIRS and ONSD outside the ICU were found. The pooled prevalence for abnormal neuromonitoring findings detected using the TCD and pupillometry were incomputable due to insufficient data. Conclusions: Neuromonitoring tools are non-invasive, less expensive, safe, and bedside available tools with a great potential for both diagnosis and monitoring of patients with COVID-19 at risk of brain derangements. However, extensive literature searching reveals that they are rarely used outside critical care settings.Systematic Review Registration: www.crd.york.ac.uk/prospero/display_record.php?RecordID=265617, identifier: CRD42021265617.

Extracorporeal cardiopulmonary resuscitation in adults: evidence and implications.

Rates of survival with functional recovery for both in-hospital and out-of-hospital cardiac arrest are notably low. Extracorporeal cardiopulmonary resuscitation (ECPR) is emerging as a modality to improve prognosis by augmenting perfusion to vital end-organs by utilizing extracorporeal membrane oxygenation (ECMO) during conventional CPR and stabilizing the patient for interventions aimed at reversing the aetiology of the arrest. Implementing this emergent procedure requires a substantial investment in resources, and even the most successful ECPR programs may nonetheless burden healthcare systems, clinicians, patients, and their families with unsalvageable patients supported by extracorporeal devices. Non-randomized and observational studies have repeatedly shown an association between ECPR and improved survival, versus conventional CPR, for in-hospital cardiac arrest in select patient populations. Recently, randomized controlled trials suggest benefit for ECPR over standard resuscitation, as well as the feasibility of performing such trials, in out-of-hospital cardiac arrest within highly coordinated healthcare delivery systems. Application of these data to clinical practice should be done cautiously, with outcomes likely to vary by the setting and system within which ECPR is initiated. ECPR introduces important ethical challenges, including whether it should be considered an extension of CPR, at what point it becomes sustained organ replacement therapy, and how to approach patients unable to recover or be bridged to heart replacement therapy. The economic impact of ECPR varies by health system, and has the potential to outstrip resources if used indiscriminately. Ideally, studies should include economic evaluations to inform health care systems about the cost-benefits of this therapy.

Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the International Severe Acute Respiratory and Emerging Infection Consortium WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study.

Due to the large number of patients with severe coronavirus disease 2019 (COVID-19), many were treated outside the traditional walls of the intensive care unit (ICU), and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the International Severe Acute Respiratory and Emerging Infection Consortium World Health Organization COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or noninvasive mechanical ventilation, high-flow nasal cannula, inotropes or vasopressors. A logistic generalised additive model was used to compare clinical outcomes among patients admitted or not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median (interquartile range (IQR), 67 (55-78) years), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 (5-19) days and was longer in patients admitted to an ICU than in those who were cared for outside the ICU (12 (6-23) days versus 8 (4-15) days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% (5797 out of 18 831) versus 39.0% (7532 out of 19 295), p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR 0.70, 95% CI 0.65-0.75; p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside an ICU.

Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the ISARIC WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study

Due to the large number of patients with severe COVID-19, many were treated outside of the traditional walls of the ICU, and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside of the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the ISARIC WHO COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or non-invasive mechanical ventilation, high-flow nasal cannula, inotropes, and vasopressors. A logistic Generalised Additive Model was used to compare clinical outcomes among patients admitted and not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median [IQR], 67 years [55, 78]), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 days (5–19) and was longer in patients admitted to an ICU than in those that were cared for outside of ICU (12 [6–23] versus 8 [4–15] days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% [5797/18831] versus 39.0% [7532/19295], p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR:0.70, 95%CI: 0.65-0.75, p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside of an ICU.

Use of Sedatives and Neuromuscular-Blocking Agents in Mechanically Ventilated Patients with COVID-19 ARDS.

OBJECTIVES: To assess differences in the use of analgesics, sedatives and neuromuscular-blocking agents (NMBA) in patients with acute respiratory distress syndrome (ARDS) due to COVID-19 or other conditions. METHODS: Retrospective observational cohort study, single-center tertiary Intensive Care Unit. COVID-19 patients with ARDS (March-May 2020) and non-COVID ARDS patients (2017-2020) on mechanical ventilation and receiving sedation for at least 48 h. RESULTS: A total of 39 patients met the inclusion criteria in each group, with similar demographics at baseline. COVID-19 patients had a longer duration of MV (median 22 (IQRs 16-29) vs. 9 (6-18) days; p < 0.01), of sedatives administration (18 (11-22) vs. 5 (4-9) days; p < 0.01) and NMBA therapy (12 (9-16) vs. 3 (2-7) days; p < 0.01). During the first 7 days of sedation, compared to non-COVID patients, COVID patients received more frequently a combination of multiple sedative drugs (76.9% vs. 28.2%; p < 0.01) and a higher NMBA regimen (cisatracurium: 3.0 (2.1-3.7) vs. 1.3 (0.9-1.9) mg/kg/day; p < 0.01). CONCLUSIONS: The duration and consumption of sedatives and NMBA was significantly increased in patients with COVID-19 related ARDS than in non-COVID ARDS. Different sedation strategies and protocols might be needed in COVID-19 patients with ARDS, with potential implications on long-term complications and drugs availability.

How to Manage Withdrawal of Sedation and Analgesia in Mechanically Ventilated COVID-19 Patients?

COVID-19 patients suffering from severe acute respiratory distress syndrome (ARDS) require mechanical ventilation (MV) for respiratory failure. To achieve these ventilatory goals, it has been observed that COVID-19 patients in particular require high regimens and prolonged use of sedatives, analgesics and neuromuscular blocking agents (NMBA). Withdrawal from analgo-sedation may induce a "drug withdrawal syndrome" (DWS), i.e., clinical symptoms of anxiety, tremor, agitation, hallucinations and vomiting, as a result of adrenergic activation and hyperalgesia. We describe the epidemiology, mechanisms leading to this syndrome and our strategies to prevent and treat it.