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      Clinical characteristics and outcomes of invasively ventilated patients with COVID-19 in Argentina (SATICOVID): a prospective, multicentre cohort study

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          Abstract

          Background

          Although COVID-19 has greatly affected many low-income and middle-income countries, detailed information about patients admitted to the intensive care unit (ICU) is still scarce. Our aim was to examine ventilation characteristics and outcomes in invasively ventilated patients with COVID-19 in Argentina, an upper middle-income country.

          Methods

          In this prospective, multicentre cohort study (SATICOVID), we enrolled patients aged 18 years or older with RT-PCR-confirmed COVID-19 who were on invasive mechanical ventilation and admitted to one of 63 ICUs in Argentina. Patient demographics and clinical, laboratory, and general management variables were collected on day 1 (ICU admission); physiological respiratory and ventilation variables were collected on days 1, 3, and 7. The primary outcome was all-cause in-hospital mortality. All patients were followed until death in hospital or hospital discharge, whichever occurred first. Secondary outcomes were ICU mortality, identification of independent predictors of mortality, duration of invasive mechanical ventilation, and patterns of change in physiological respiratory and mechanical ventilation variables. The study is registered with ClinicalTrials.gov, NCT04611269, and is complete.

          Findings

          Between March 20, 2020, and Oct 31, 2020, we enrolled 1909 invasively ventilated patients with COVID-19, with a median age of 62 years [IQR 52–70]. 1294 (67·8%) were men, hypertension and obesity were the main comorbidities, and 939 (49·2%) patients required vasopressors. Lung-protective ventilation was widely used and median duration of ventilation was 13 days (IQR 7–22). Median tidal volume was 6·1 mL/kg predicted bodyweight (IQR 6·0–7·0) on day 1, and the value increased significantly up to day 7; positive end-expiratory pressure was 10 cm H 2O (8–12) on day 1, with a slight but significant decrease to day 7. Ratio of partial pressure of arterial oxygen (PaO 2) to fractional inspired oxygen (FiO 2) was 160 (IQR 111–218), respiratory system compliance 36 mL/cm H 2O (29–44), driving pressure 12 cm H 2O (10–14), and FiO 2 0·60 (0·45–0·80) on day 1. Acute respiratory distress syndrome developed in 1672 (87·6%) of patients; 1176 (61·6%) received prone positioning. In-hospital mortality was 57·7% (1101/1909 patients) and ICU mortality was 57·0% (1088/1909 patients); 462 (43·8%) patients died of refractory hypoxaemia, frequently overlapping with septic shock (n=174). Cox regression identified age (hazard ratio 1·02 [95% CI 1·01–1·03]), Charlson score (1·16 [1·11–1·23]), endotracheal intubation outside of the ICU (ie, before ICU admission; 1·37 [1·10–1·71]), vasopressor use on day 1 (1·29 [1·07–1·55]), D-dimer concentration (1·02 [1·01–1·03]), PaO 2/FiO 2 on day 1 (0·998 [0·997–0·999]), arterial pH on day 1 (1·01 [1·00–1·01]), driving pressure on day 1 (1·05 [1·03–1·08]), acute kidney injury (1·66 [1·36–2·03]), and month of admission (1·10 [1·03–1·18]) as independent predictors of mortality.

          Interpretation

          In patients with COVID-19 who required invasive mechanical ventilation, lung-protective ventilation was widely used but mortality was high. Predictors of mortality in our study broadly agreed with those identified in studies of invasively ventilated patients in high-income countries. The sustained burden of COVID-19 on scarce health-care personnel might have contributed to high mortality over the course of our study in Argentina. These data might help to identify points for improvement in the management of patients in middle-income countries and elsewhere.

          Funding

          None.

          Translation

          For the Spanish translation of the Summary see Supplementary Materials section.

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          Most cited references32

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          Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

          Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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            Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

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              Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

              Abstract Background Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death. Methods In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the preliminary results of this comparison. Results A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55). Conclusions In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936; ISRCTN number, 50189673.)
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                Author and article information

                Journal
                Lancet Respir Med
                Lancet Respir Med
                The Lancet. Respiratory Medicine
                Elsevier Ltd.
                2213-2600
                2213-2619
                2 July 2021
                2 July 2021
                Affiliations
                [a ]Hospital Interzonal de Agudos General San Martín, Buenos Aires, Argentina
                [b ]Sanatorio Las Lomas, Buenos Aires, Argentina
                [c ]Hospital Juan A Fernández, Buenos Aires, Argentina
                [d ]Sanatorio Anchorena, Buenos Aires, Argentina
                [e ]Hospital Provincial Dr Castro Rendón, Neuquén, Argentina
                [f ]Sanatorio Güemes, Buenos Aires, Argentina
                [g ]Hospital A Posadas, Buenos Aires, Argentina
                [h ]Hospital Santojanni, Buenos Aires, Argentina
                [i ]Sanatorio Anchorena San Martín, Buenos Aires, Argentina
                [j ]Hospital Francisco Lopez Lima, Río Negro, Argentina
                [k ]Sanatorio Otamendi, Buenos Aires, Argentina
                [l ]Sanatorio de Los Arcos, Buenos Aires, Argentina
                [m ]Hospital Dr F J Muñiz, Buenos Aires, Argentina
                [n ]Complejo Médico de la Policía Federal Argentina Churruca Visca, Buenos Aires, Argentina
                [o ]Sociedad Argentina de Terapia Intensiva, Buenos Aires, Argentina
                Author notes
                [* ]Correspondence to: Dr Elisa Estenssoro, Servicio de Terapia Intensiva, Hospital Interzonal de Agudos General San Martín, Calle 42 No. 577, 1900 La Plata, Provincia de Buenos Aires, Argentina
                [†]

                Group members are listed in appendix 2

                Article
                S2213-2600(21)00229-0
                10.1016/S2213-2600(21)00229-0
                8253540
                34224674
                7d13cdaa-2e98-4b15-9e40-414ce6e639de
                © 2021 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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