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Original article
Association between different corticosteroid regimens used in severe SARS-CoV-2 infection and short-term mortality: retrospective cohort study
Asociación entre diferentes pautas de corticoides empleadas en la infección grave por SARS-CoV-2 y la mortalidad a corto plazo: estudio de cohortes retrospectivo
A. González-Castro
Corresponding author
e409@humv.es

Corresponding author.
, A. Fernandez, E. Cuenca-Fito, Y. Peñasco, J. Ceña, J.C. Rodríguez Borregán
Servicio de Medicina Intensiva, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria, Spain
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especially in the hyperinflammatory state &#40;&#8220;cytokine storm&#8221;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In this context&#44; following the publication of the RECOVERY trial results&#44; it was shown that the use of corticosteroids&#44; specifically dexamethasone at a dose of 6<span class="elsevierStyleHsp" style=""></span>mg per day&#44; resulted in a significant 11&#37; reduction in patient mortality&#46; As a result of these findings&#44; the World Health Organisation &#40;WHO&#41; announced that corticosteroids be considered the gold standard treatment for severe cases of SARS-CoV-2&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">However&#44; methylprednisolone has a higher lung tissue-to-plasma ratio in experimental animals compared to dexamethasone&#44; which may indicate a different action on lung injury&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In light of the need for a better understanding of the effects of corticosteroids in critically ill patients with COVID-19&#44; to provide information on the efficacy and safety of different corticosteroids in the management of critically ill patients with COVID-19&#44; the aim of this study is to analyse the impact of dexamethasone and methylprednisolone therapy on short-term survival &#40;28 days&#41; of patients requiring intensive care unit &#40;ICU&#41; admission due to SARS-CoV-2 infection&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Method</span><p id="par0025" class="elsevierStylePara elsevierViewall">Retrospective&#44; observational&#44; and analytical study which included adult patients admitted to the COVID area with a confirmed diagnosis of SARS-CoV-2 infection by polymerase chain reaction &#40;PCR&#41; in respiratory tract cells from the intensive care unit between March 2020 and June 2021&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Data were obtained from the patient cohort of the COVID patient registry of the intensive care medicine department&#44; approved by the local research ethics committee &#40;2020&#46;250&#41;&#44; and with patient&#47;representative consent &#40;written and&#47;or telephonic&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The clinical-demographic variables of the patients were recorded&#58; date of admission to the ICU&#44; age in calendar years at the time of admission to the ICU&#44; sex &#40;dichotomous variable male or female&#41;&#44; reason for the main clinical admission being acute respiratory failure &#40;as dichotomous variable yes&#47;no&#41;&#59; comorbidities &#40;as dichotomous variables yes&#47;no&#59; hypertension &#40;HTN&#41;&#58; diagnosed in the clinical history prior to the current admission&#59; obesity&#58; body mass index previously diagnosed in the clinical history or described as &#8805; 30&#59; diabetes mellitus&#58; diagnosed in the clinical history prior to the current admission &#40;no differentiation into type I or II&#41;&#59; dyslipidaemia&#58; diagnosed in the clinical history as hypercholesterolaemia and&#47;or hypertriglyceridaemia prior to the current admission&#59; smoker&#58; diagnosed in the clinical history prior to the current admission as active smoker or collected during history taking from patient or relatives&#59; biomarkers analysed &#40;first value&#41; as continuous variables collected in the in the first 24<span class="elsevierStyleHsp" style=""></span>h from admission to ICU&#58; creatine kinase &#40;CK in units&#47;litre &#91;U&#47;L&#93;&#44; reference range of normality&#58; 46&#8211;171&#41;&#44; D-dimer &#40;DD in ng&#47;m&#44; normal reference range&#58; 0&#8211;500&#41;&#59; determination of arterial oxygen pressure&#47;inspiratory oxygen fraction &#40;P&#47;F&#41; ratio as a continuous variable at ICU admission&#59; therapies required during ICU admission as dichotomous variables yes&#47;no&#58; high-flow nasal cannula &#40;HFNC&#41;&#44; mechanical ventilation &#40;MV&#41;&#44; anticoagulation dose with prophylactic characteristics according to patient weight&#44; use of antibiotherapy for prophylactic purposes&#44; use of prone position as a therapeutic measure&#44; use of corticosteroids as antiviral treatment&#44; need for vasoactive and&#47;or inotropic drugs due to septic shock&#44; use of continuous renal replacement therapy &#40;CRRT&#41; due to renal failure&#44; and evolutionary variables&#58; days of mechanical ventilation in days as continuous variable&#44; development of pulmonary thromboembolism &#40;PTE&#41; confirmed by computed tomography &#40;CT&#41; as dichotomous variable yes&#47;no&#44; development of ventilator-associated tracheobronchitis and ventilator-associated pneumonia &#40;VAT and VAP&#41; as dichotomous variable yes&#47;no&#44; need for tracheostomy &#40;according to clinical criteria&#41; due to prolongation of MV as dichotomous variable yes&#47;no&#44; ICU stay in days as continuous variable&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Patients were categorised into 4 groups&#44; 1&#41; patients who did not receive corticosteroid treatment during their stay in the ICU&#44; 2&#41; patients treated with dexamethasone 6<span class="elsevierStyleHsp" style=""></span>mg daily for up to 10 days&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> 3&#41; patients who received dexamethasone in doses higher than 6<span class="elsevierStyleHsp" style=""></span>mg daily&#44;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> and 4&#41; patients managed with low doses of methylprednisolone &#40;40&#8211;80<span class="elsevierStyleHsp" style=""></span>mg daily&#41; for a period of 3 to 5 days&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">We performed a descriptive analysis of the sample&#58; for continuous variables&#44; the Shapiro&#8211;Wilk test was used as a test of normality&#46; Continuous variables with a normal distribution are described as mean and standard deviation &#40;SD&#41;&#44; while continuous variables with a non-normal distribution are expressed as median and their 25&#8211;75 percentiles &#40;p25&#8211;75&#41;&#46; Pearson&#8217;s &#967;<span class="elsevierStyleSup">2</span> test or Fisher&#8217;s exact test were used to compare between groups to compare proportions&#44; and the Kruskal&#8211;Wallis test to compare continuous variables&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">A Cox proportional hazards regression model was used in the study of risk factors for 28-day ICU mortality&#44; entering variables with a value of p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;1 in the bivariate analysis against 28-day mortality&#46; Results are shown by the risk ratio &#40;RR&#41; and its 95&#37; confidence interval &#40;95&#37; CI&#41; for Cox regression&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Survival analysis was performed using the Kaplan&#8211;Meier method and comparisons were made using the long-rank test&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Statistical software MedCalc&#174;&#44; version 19&#46;5&#46;3 &#40;MedCalc Software Ltd&#44; Ostende&#44; Belgium&#59; <a href="https://www.medcalc.org">https&#58;&#47;&#47;www&#46;medcalc&#46;org</a>&#59; 2020&#41; was used for calculations and statistical analyses&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0065" class="elsevierStylePara elsevierViewall">Over the study period&#44; 565 patients were admitted to the ICU with a diagnosis of SARS-CoV-2 infection or high suspicion of SARS-CoV-2&#46; Twenty-six patients were excluded because SARS-CoV-2 infection could not be microbiologically confirmed&#46; The main baseline and clinical-epidemiological characteristics of the remaining 539 patients are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">As shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#44; age showed a significant difference between the corticosteroid treatment groups &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;03&#41;&#44; and no significant differences were found in the main comorbidities&#44; except for obesity &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41;&#46; Regarding laboratory data on ICU admission&#44; significant differences were observed in creatine kinase &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41; and D-dimer &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41; values between treatment groups&#46; With regard to adjuvant antiviral treatments and therapies during ICU admission&#44; significant differences were observed&#46; Plasma use was more frequent in the group treated with dexamethasone at a dose of 6<span class="elsevierStyleHsp" style=""></span>mg&#47;day &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41;&#44; while the need for invasive mechanical ventilation &#40;IMV&#41; was higher in the group treated with methylprednisolone &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41;&#46; ICU stay in days showed a significant difference between treatment groups &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41;&#46; In addition&#44; 28-day ICU mortality was significantly lower in the groups treated with dexamethasone at a dose of 6<span class="elsevierStyleHsp" style=""></span>mg&#47;day &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41; and methylprednisolone &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41; compared to the group that did not receive corticosteroid treatment&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">For the dexamethasone dose of 6<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; an RR of &#46;40 &#40;95&#37; CI &#46;15&#8211;1&#46;02&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41; was found&#44; suggesting an association with lower short-term mortality&#46; For a dexamethasone dose greater than 6<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; the RR was &#46;54 &#40;95&#37; CI&#58; &#46;21&#8211;1&#46;37&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;19&#41;&#44; indicating a trend towards a beneficial effect&#44; although it was not statistically significant&#46; For the methylprednisolone dose &#40;40&#8211;80<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#44; an RR of &#46;51 &#40;95&#37; CI&#58; &#46;20&#8211;1&#46;27&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;15&#41; was obtained&#44; which was not statistically significant either&#46; Regarding patient characteristics&#44; age showed a significant association with short-term mortality in the ICU &#40;RR&#58; 1&#46;06&#59; 95&#37; CI&#58; 1&#46;02&#8211;1&#46;10&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41;&#46; For each year of life&#44; a slight increase in mortality risk was observed&#46; However&#44; the presence of obesity did not show a significant association with mortality &#40;RR&#58; 1&#46;66&#59; 95&#37; CI&#58; &#46;76&#8211;3&#46;62&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;19&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">In the survival analysis&#44; comparison using Kaplan&#8211;Meier curves at 28 days follow-up&#44; showed a difference between groups as seen in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> &#40;long-rank test&#58; p<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0085" class="elsevierStylePara elsevierViewall">In our analysis&#44; 1&#41; patients who received corticosteroid treatment had a longer survival at 28 days compared to patients who did not receive corticosteroid treatment&#44; and 2&#41; both dexamethasone at a dose of 6<span class="elsevierStyleHsp" style=""></span>mg&#47;day and low-dose methylprednisolone appear to be effective in the treatment of severe SARS-CoV-2 disease requiring ICU admission&#44; in terms of 28-day mortality&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">However&#44; in our analysis it should be considered that the group of patients not treated with corticosteroids show significantly higher severity criteria &#40;lower PaO2&#47;FiO2 ratio&#44; higher CK&#44; and DD&#41; on admission to the ICU&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">There is heterogeneity in the use of glucocorticoids and their effect on mortality in acute lung injury induced by viral diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#8211;16</span></a> High doses of glucocorticoids may delay viral clearance and increase mortality and the risk of secondary infections&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a> However&#44; in patients with severe SARS-CoV-2 disease&#44; short-duration glucocorticoid regimens have proven beneficial and safe&#44; and do not behave as an independent risk factor for prolonged viral RNA shedding&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;20</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">After publication of the RECOVERY trial&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> dexamethasone became the standard treatment for the most severely ill patients&#46; The study showed that the use of dexamethasone resulted in lower mortality among patients undergoing mechanical ventilation or receiving high concentrations of oxygen&#44; but not among those not receiving respiratory support&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The effect of corticosteroids as a whole was studied using data from a prospective meta-analysis that pooled data from 7 randomised clinical trials &#40;RCTs&#41;&#46; In their results&#44; the odds ratio &#40;OR&#41; for association with mortality was &#46;64 &#40;95&#37; CI &#46;50&#8211;&#46;82&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; for dexamethasone compared to usual care or placebo &#40;3 trials&#44; 1282 patients&#44; and 527 deaths&#41;&#44; while it was &#46;69 &#40;95&#37; CI &#46;43&#8211;1&#46;12&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;13&#41; for hydrocortisone &#40;3 trials&#44; 374 patients&#44; and 94 deaths&#41; and &#46;91 &#40;95&#37; CI &#46;29&#8211;2&#46;87&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;87&#41; for hydrocortisone and methylprednisolone respectively &#40;1 trial&#44; 47 patients and 26 deaths&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">A subsequent comprehensive analysis of 11 RCTs with 8019 hospitalised participants with COVID-19 evaluated the efficacy of systemic corticosteroids together with standard care compared to standard care alone&#44; or standard care plus placebo&#46; We found that systemic corticosteroids together with standard care probably slightly reduce all-cause mortality up to 30 days&#44; although the evidence on mortality up to 120 days was unclear&#46; In addition&#44; systemic corticosteroids appear to slightly increase the likelihood of clinical improvement at 28 days&#46; For serious adverse events&#44; nosocomial infections and invasive mycoses&#44; there was insufficient evidence for conclusive analyses&#46; When comparing different types and doses of corticosteroids&#44; we found that methylprednisolone compared to dexamethasone showed no significant difference in mortality&#46; High-dose dexamethasone &#40;12<span class="elsevierStyleHsp" style=""></span>mg or more&#41; could reduce mortality up to 30 days&#44; but no clear conclusion was found on mortality up to 120 days and clinical improvement at 28 days&#46; Subgroup analyses were performed to explore equity in the effects of corticosteroids&#46; It was observed that patients under 70 years might benefit more from corticosteroids compared to those aged over 70 years&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">The limitations of our study are those inherent to retrospective studies&#58; under-reporting and variability among professionals&#46; In this regard&#44; the lack of any variable &#40;especially analytical tests&#41; or a more specific categorisation of some of them &#40;for example&#44; CK or DD values&#41; that could influence the final results should be considered a limitation of the study&#46; In addition&#44; these data are analysed from a single centre&#44; with the difficulty in external validation of the conclusions that this always entails&#46; Another relevant limitation of this study is the absence of an explicit consideration of the possible impact of the timing of patient admission in relation to mortality outcomes&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">In this study&#44; certain variables relevant to corticosteroid treatment in patients hospitalised with COVID-19 were identified and analysed&#46; However&#44; it is possible that other variables not considered in this analysis may have had an impact on the results&#46; Some potential additional variables that could have had an influence include differences in patient comorbidities&#44; disease duration and severity&#44; individual response to corticosteroids&#44; and the presence of other concurrent therapies or medications&#46; In addition&#44; genetic characteristics and access to care may also play a role in the variability of outcomes&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In order to improve the understanding and applicability of these findings&#44; future research should consider including a wider range of relevant variables and conducting more detailed analyses to better understand the impact of corticosteroids in patients with COVID-19&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Based on the data presented and the analysis of the literature&#44; we can conclude that the use of systemic corticosteroids in conjunction with standard care may have a beneficial effect in reducing short-term mortality in patients hospitalised with COVID-19&#46; However&#44; longer-term effects and adverse events require further investigation&#46; In addition&#44; outcomes may vary in different patient subgroups&#44; emphasising the importance of considering equity factors in clinical decision-making&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Key concepts</span><p id="par0165" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0135" class="elsevierStylePara elsevierViewall">During the COVID pandemic&#44; no standard&#47;uniform corticosteroid regimen was established for the treatment of severely ill patients&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0140" class="elsevierStylePara elsevierViewall">Dexamethasone and methylprednisolone were the most commonly used corticosteroids in different regimens&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0145" class="elsevierStylePara elsevierViewall">Patients who received corticosteroid treatment had longer survival at 28 days compared to patients who did not receive corticosteroid treatment</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0150" class="elsevierStylePara elsevierViewall">A possible efficacy of both dexamethasone at a dose of 6<span class="elsevierStyleHsp" style=""></span>mg&#47;day and low-dose methylprednisolone in the treatment of severe SARS-CoV-2 disease requiring ICU admission is suggested in relation to 28-day mortality&#46;</p></li></ul></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Funding</span><p id="par0155" class="elsevierStylePara elsevierViewall">No funding was received for this manuscript&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflict of interests</span><p id="par0160" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">During the SARS-CoV-2 pandemic&#44; several corticosteroid regimens have been used in the treatment of the disease&#44; with disparate results according to drug and regimen used&#46; For this reason&#44; we wanted to analyze differences in early mortality derived from the use of different regimens of dexamethasone and methylprednisolone in SARS-CoV-2 infection in critically ill patients requiring admission to an ICU&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Method</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Observational&#44; analytical and retrospective study&#44; in an intensive care unit of a third-level university hospital&#44; &#40;March 2020 and June 2021&#41;&#46; Adult patients &#40;&#62;18 years old&#41; who were admitted consecutively for proven SARS-CoV-2 infection were included&#46; The association with mortality in ICU at 28 days&#44; different corticosteroid regimens used&#44; was analyzed using a Cox proportional risk regression model&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Data from a cohort of 539 patients were studied&#46; Patient age &#40;RR&#58; 1&#46;06&#59; 95&#37; CI&#58; 1&#46;02&#8211;1&#46;10&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#60;0&#46;01&#41; showed a significant association with 28-day mortality in the ICU&#46; In the comparison of the different corticosteroid regimens analyzed&#44; taking as a reference those patients who did not receive corticosteroid treatment&#44; the dose of dexamethasone of 6<span class="elsevierStyleHsp" style=""></span>mg&#47;day showed a clear trend towards statistical significance as a protector of mortality at 28 days in the ICU &#40;RR&#58; 0&#46;40&#44; 95&#37; CI&#58; 0&#46;15&#8211;1&#46;02&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; The dose of dexamethasone of 6<span class="elsevierStyleHsp" style=""></span>mg&#47;day and low doses of methylprednisolone show a similar association with survival at 28 days &#40;OR&#58; 1&#46;19&#59; 95&#37; CI&#58; 0&#46;63&#8211;2&#46;26&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">The use of corticosteroids has been associated with better mortality outcomes in severe cases of SARS-CoV-2 infection&#46; However&#44; the therapeutic benefits of corticosteroids are not limited to dexamethasone alone&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Method"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Durante la pandemia por SARS-CoV-2&#44; varias pautas de corticoides han sido utilizadas en el tratamiento de la enfermedad&#44; con resultados dispares seg&#250;n f&#225;rmaco y pauta utilizada&#46; Por este motivo hemos querido analizar diferencias en la mortalidad temprana derivadas del empleo de diferentes pautas de dexametasona y metilprednisolona en infecci&#243;n por SARS-CoV-2 en pacientes graves que requieren ingreso en una unidad de cuidados intensivos &#40;UCI&#41;&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todo</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional&#44; anal&#237;tico y retrospectivo llevado a cabo en una unidad de cuidados intensivos de un hospital universitario de tercer nivel&#44; entre marzo de 2020 y junio de 2021&#46; Se incluyeron pacientes adultos &#40;&#62;18 a&#241;os&#41; que ingresaron de forma consecutiva debido a una infecci&#243;n confirmada por el virus SARS-CoV-2&#46; Se evalu&#243; la asociaci&#243;n entre diferentes pautas de corticoides utilizadas y la mortalidad en la UCI a los 28 d&#237;as mediante un modelo de regresi&#243;n de riesgos proporcionales de Cox&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Cohorte de 539 pacientes donde la edad de los pacientes mostr&#243; una asociaci&#243;n significativa con la mortalidad a los 28 d&#237;as en la UCI &#40;RR&#58; 1&#44;06&#59; IC 95&#37;&#58; 1&#44;02-1&#44;10&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#46; Al analizar las diferentes pautas de corticoides utilizadas&#44; se identific&#243; una posible tendencia en la asociaci&#243;n entre la dosis de dexametasona de 6<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#237;a y una menor mortalidad a los 28 d&#237;as en la UCI&#44; con un RR de 0&#44;40 &#40;IC 95&#37;&#58; 0&#44;15-1&#44;02&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46; Por otro lado&#44; las dosis de dexametasona mayores a 6<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#237;a y las dosis bajas de metilprednisolona mostraron una tendencia a reducir la mortalidad&#44; aunque no alcanzaron significaci&#243;n estad&#237;stica &#40;RR&#58; 0&#44;54&#59; IC 95&#37;&#58; 0&#44;21-1&#44;37&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;19 y RR&#58; 0&#44;51&#59; IC 95&#37;&#58; 0&#44;20-1&#44;27&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;15&#44; respectivamente&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">El estudio sugiere que la edad y la dosis de dexametasona de 6<span class="elsevierStyleHsp" style=""></span>mg&#47;d&#237;a podr&#237;an ser factores importantes en la mortalidad a los 28 d&#237;as en pacientes con infecci&#243;n por SARS-CoV-2 en UCI&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Introducci&#243;n"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todo"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
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      0 => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
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        "detalles" => array:1 [
          0 => array:3 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Survival analysis &#40;Kaplan&#8211;Meier&#41; referring to survival at 28 days in the 4 groups established&#46; Survival curves at 28 days for patients categorised into 4 groups&#58; 1&#41; patients who did not receive corticosteroid treatment during their ICU stay&#59; 2&#41; patients treated with dexamethasone 6<span class="elsevierStyleHsp" style=""></span>mg daily for up to 10 days&#59; 3&#41; patients who received dexamethasone in doses higher than 6<span class="elsevierStyleHsp" style=""></span>mg daily&#44; and 4&#41; patients managed with low doses of methylprednisolone &#40;40&#8211;80<span class="elsevierStyleHsp" style=""></span>mg daily&#41; for a period of 3 to 5 days&#46;</p>"
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      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
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            "identificador" => "at0330"
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          "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">DM&#44; diabetes mellitus&#59; ECMO&#44; extracorporeal membrane oxygenation&#59; HT&#44; hypertension&#59; HFNC&#44; high-flow nasal cannula&#59; ICU&#44; intensive care unit&#59; IMV&#44; invasive mechanical ventilation&#59; iNO&#44; inhaled nitric oxide&#59; RRT&#44; renal replacement techniques&#59; SD&#44; standard deviation&#59; SOFA&#44; Sequential Organ Failure Assessment score&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variables&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>539&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Age &#40;mean &#91;SD&#93;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63 &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sex</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Males &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">368 &#40;68&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Main comorbidities</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>HTN &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">274 &#40;50&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>DM &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">117 &#40;21&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Obesity &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">113 &#40;21&#46;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dyslipidaemia &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">188 &#40;34&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Smoker &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">170 &#40;31&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">SOFA score on admission to ICU &#40;mean &#91;SD&#93;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> on admission to ICU &#40;median &#91;q25&#8211;75&#93;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">139 &#40;103&#8211;180&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Laboratory data on admission to ICU</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Creatine kinase &#40;median &#91;q25&#8211;75&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">109 &#40;54&#8211;302&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>D-dimer &#40;median &#91;q25&#8211;75&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">917 &#40;553&#8211;1883&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Treatment used during ICU stay</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Tocilizumab and corticosteroid combination immunomodulatory therapy &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">395 &#40;73&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Use of prone positioning &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">233 &#40;57&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Use of HNFC on admission to ICU &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">292 &#40;58&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Need for IMV &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">370 &#40;70&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Need for vasopressors &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">242 &#40;44&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Use of ECMO &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Use of iNO therapy &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32 &#40;5&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Need for RRT &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 &#40;4&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hyperimmune plasma treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">180 &#40;33&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Treatment with remdesivir&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64 &#40;11&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Stay in ICU in days &#40;median &#91;q25&#8211;75&#93;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;5&#8211;18&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Mortality in ICU at 28 days &#40;n &#91;&#37;&#93;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70 &#40;13&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">DM&#44; Diabetes Mellitus&#59; ECMO&#44; Extracorporeal Membrane Oxygenation&#59; HFNC&#44; High-flow nasal cannula&#59; HTN&#44; Hypertension&#59; ICU&#44; Intensive Care Unit&#59; IMV&#44; Invasive mechanical ventilation&#59; iNO&#44; inhaled nitric oxide&#59; RRT&#44; Renal replacement techniques&#59; VAT&#47;VAP&#44; Ventilator-associated tracheobronchitis&#47; pneumonia&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variables&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No corticosteroid use&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dexamethasone 6<span class="elsevierStyleHsp" style=""></span>mg&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dexamethasone &#62;6<span class="elsevierStyleHsp" style=""></span>mg&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Methylprednisolone 40&#8211;80<span class="elsevierStyleHsp" style=""></span>mg&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p-Value<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>123&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>196&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>129&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Age &#40;median &#91;p25&#8211;75&#93;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66 &#40;54&#8211;73&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64 &#40;54&#8211;71&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">69 &#40;57&#8211;74&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68 &#40;58&#8211;74&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sex</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Males &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">79 &#40;64&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">129 &#40;66&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64 &#40;70&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">96 &#40;74&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Main comorbidities</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>HTN &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57 &#40;46&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">106 &#40;54&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39 &#40;43&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72 &#40;56&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>DM &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#40;23&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47 &#40;24&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;16&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27 &#40;21&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Obesity &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;10&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 &#40;25&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;15&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37 &#40;29&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dyslipidaemia &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Smoker &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> on admission to ICU &#40;median &#91;q25&#8211;75&#93;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">112 &#40;89&#8211;184&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">146 &#40;117&#8211;180&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">138 &#40;99&#8211;177&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">145 &#40;116&#8211;187&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#46;02&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " colspan="6" align="left" valign="\n
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                  \t\t\t\t">Laboratory data on admission to ICU</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Creatine kinase &#40;median &#91;q25&#8211;75&#93;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">308 &#40;92&#8211;705&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">101 &#40;56&#8211;215&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">72 &#40;43&#8211;193&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">81 &#40;47&#8211;187&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#60;&#46;01&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>D-dimer &#40;median &#91;q25&#8211;75&#93;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&#46;545&#40;1&#46;567&#8211;19&#46;000&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">743 &#40;522&#8211;1&#46;148&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">899 &#40;543&#8211;1&#46;734&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">780 &#40;478&#8211;1&#46;310&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#60;&#46;01&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Adjuvant antiviral treatments</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Remdesivir n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Plasma&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">86 &#40;44&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#60;&#46;01&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Immunomodulatory treatment with tocilizumab &#40;n &#91;&#37;&#93;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">14 &#40;11&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">33 &#40;17&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">17 &#40;19&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">32 &#40;25&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Treatment during admission to ICU</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Use of HFNC on admission to ICU &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">32 &#40;26&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">137 &#40;70&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">44 &#40;48&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">79 &#40;61&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#60;&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Need for IMV &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">84 &#40;68&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">135 &#40;69&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">76 &#40;83&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">75 &#40;58&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&#60;&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Prone positioning &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">61 &#40;49&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">74 &#40;38&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">51 &#40;56&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Use of ECMO &#40;n &#91;&#37;&#93;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Stay in ICU in days &#40;median &#91;p25&#8211;75&#93;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8 &#40;3-16&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">9 &#40;5-18&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">11 &#40;8-19&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8 &#40;4-15&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">26 &#40;21&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Methylprednisolone dose of &#40;40&#8211;80<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;20&#8211;1&#46;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#40;per year of life&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;02&#8211;1&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#60;&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Presenting obesity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;76&#8211;3&#46;62&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Creatine kinase value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;99&#8211;1&#46;00&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D-dimer value on admission&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;00&#8211;1&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;94&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PaO<span class="elsevierStyleInf">2</span>&#47;FiO<span class="elsevierStyleInf">2</span> on admission to ICU&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;99&#8211;1&#46;00&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Use of tocilizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;30&#8211;1&#46;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Use of hyperimmune plasma&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;33&#8211;1&#46;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prone positioning therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;37&#8211;1&#46;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Use of RRT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;28&#8211;2&#46;51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Onset of VAP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;51&#8211;2&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Use of HFNC on admission to ICU&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;42&#8211;1&#46;52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Need for IMV during admission&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;70&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#46;28&#8211;1&#46;75&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#46;43&nbsp;\t\t\t\t\t\t\n
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                  """
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                      "titulo" => "Dexamethasone treatment for the acute respiratory distress syndrome&#58; a multicentre&#44; randomised controlled trial"
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                          "etal" => true
                          "autores" => array:6 [
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                            4 => "T&#46; Mu&#241;oz"
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                            0 => "L&#46; Lansbury"
                            1 => "C&#46; Rodrigo"
                            2 => "J&#46; Leonardi-Bee"
                            3 => "J&#46; Nguyen-Van-Tam"
                            4 => "W&#46;S&#46; Lim"
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                    0 => array:2 [
                      "doi" => "10.1002/14651858.CD010406.pub3"
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                      "titulo" => "Epidemic and emerging coronaviruses &#40;severe acute respiratory syndrome and Middle East respiratory syndrome&#41;"
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                          "etal" => false
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                      "doi" => "10.1016/j.ccm.2016.11.007"
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                        "tituloSerie" => "Clin Chest Med"
                        "fecha" => "2017"
                        "volumen" => "38"
                        "paginaInicial" => "71"
                        "paginaFinal" => "86"
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                            3 => "E&#46;K&#46;O&#46; Ng"
                            4 => "A&#46; Wu"
                            5 => "R&#46;W&#46;K&#46; Chiu"
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                    0 => array:2 [
                      "doi" => "10.1016/j.jcv.2004.07.006"
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                        "tituloSerie" => "J Clin Virol"
                        "fecha" => "2004"
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Article information
ISSN: 23411929
Original language: English
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