Impact of Early Corticosteroids on 60-day Mortality in Critically Ill Patients with COVID-19: A Multicenter Cohort Study of the OUTCOMEREA Network

Dupuis, Claire; Montmollin, Étienne de; Buetti, Niccolò; Goldgran-Tolédano, Dany; Reignier, Jean; Schwebel, Carole; Domitile, Julien; Neuville, Mathilde; Ursino, Moreno; Siami, Shidasp; Ruckly, Stéphane; Alberti, Corinne; Mourvillier, Bruno; Bailly, Sébastien; Laurent, Virginie; Gainnier, Marc; Souweine, Bertrand; Timsit, Jean‐François

doi:10.21203/rs.3.rs-293856/v1

Cited by 10 publications

(8 citation statements)

References 41 publications

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“…It may be that prolonged and highdose courses of corticosteroids explain why our results diverge from those reported in clinical trials [39,40]. Other observational studies have found a relationship between corticosteroid use and subsequent pneumonia in single centre [42] and multi-centre cohorts [34,43], with the Dupuis and colleagues study noting a relationship between steroid dose and infection risk [34]. It is possible that steroids were prescribed because of secondary infection i.e.…”

Section: Discussioncontrasting

confidence: 51%

“…In this study, corticosteroids were not associated with increased survival, so it is unlikely that their use increased infection due to patients surviving long enough to develop an infection in ICU. The finding of increased unadjusted mortality amongst patients receiving steroids may reflect differences between patients selected for corticosteroid therapy, although other reports have noted similar effects even after adjusting for clinical variables [33,34].…”

Section: Discussionmentioning

confidence: 86%

“…Factors evaluated for association with ICU-AI are shown in Table 2. ICU-AI was associated with longer ICU length of stay (median 24 days (IQR [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] days vs 11 days (IQR 6-17) (p < 0.001), as was infection with MDRO (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43) days for MDRO vs 23 days (IQR [15][16][17][18][19][20][21][22][23][24][25][26][27]…”

Section: Factors Associated With Icu-aimentioning

confidence: 99%

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Co-infection and ICU-acquired infection in COVID-19 ICU patients: a secondary analysis of the UNITE-COVID data set

Morris

Köhler²,

Corte³

et al. 2022

Crit Care

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Background The COVID-19 pandemic presented major challenges for critical care facilities worldwide. Infections which develop alongside or subsequent to viral pneumonitis are a challenge under sporadic and pandemic conditions; however, data have suggested that patterns of these differ between COVID-19 and other viral pneumonitides. This secondary analysis aimed to explore patterns of co-infection and intensive care unit-acquired infections (ICU-AI) and the relationship to use of corticosteroids in a large, international cohort of critically ill COVID-19 patients. Methods This is a multicenter, international, observational study, including adult patients with PCR-confirmed COVID-19 diagnosis admitted to ICUs at the peak of wave one of COVID-19 (February 15th to May 15th, 2020). Data collected included investigator-assessed co-infection at ICU admission, infection acquired in ICU, infection with multi-drug resistant organisms (MDRO) and antibiotic use. Frequencies were compared by Pearson’s Chi-squared and continuous variables by Mann–Whitney U test. Propensity score matching for variables associated with ICU-acquired infection was undertaken using R library MatchIT using the “full” matching method. Results Data were available from 4994 patients. Bacterial co-infection at admission was detected in 716 patients (14%), whilst 85% of patients received antibiotics at that stage. ICU-AI developed in 2715 (54%). The most common ICU-AI was bacterial pneumonia (44% of infections), whilst 9% of patients developed fungal pneumonia; 25% of infections involved MDRO. Patients developing infections in ICU had greater antimicrobial exposure than those without such infections. Incident density (ICU-AI per 1000 ICU days) was in considerable excess of reports from pre-pandemic surveillance. Corticosteroid use was heterogenous between ICUs. In univariate analysis, 58% of patients receiving corticosteroids and 43% of those not receiving steroids developed ICU-AI. Adjusting for potential confounders in the propensity-matched cohort, 71% of patients receiving corticosteroids developed ICU-AI vs 52% of those not receiving corticosteroids. Duration of corticosteroid therapy was also associated with development of ICU-AI and infection with an MDRO. Conclusions In patients with severe COVID-19 in the first wave, co-infection at admission to ICU was relatively rare but antibiotic use was in substantial excess to that indication. ICU-AI were common and were significantly associated with use of corticosteroids. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021). Graphical abstract

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Section: Discussioncontrasting

confidence: 51%

Section: Discussionmentioning

confidence: 86%

Section: Factors Associated With Icu-aimentioning

confidence: 99%

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Co-infection and ICU-acquired infection in COVID-19 ICU patients: a secondary analysis of the UNITE-COVID data set

Morris

Köhler²,

Corte³

et al. 2022

Crit Care

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“…These short-term protective effects have also been found for the subgroup of patients aged < 60 years, similar findings as those observed in the RECOVERY trial which showed protective effects of corticosteroids for patients younger than 70 years. However, a multicentre study conducted in 303 critically ill COVID-19 patients found opposite results to ours, reporting that early corticosteroid administration was associated with a lower mortality rate in patients aged ≥ 60 years [40]. The contradictory results might be due to a different population than ours with only onethird of included patients under invasive mechanical ventilation.…”

Section: Discussioncontrasting

confidence: 86%

Corticosteroid treatment and mortality in mechanically ventilated COVID-19-associated acute respiratory distress syndrome (ARDS) patients: a multicentre cohort study

Moreno

Carbonell

Martín‐Loeches

et al. 2021

Ann. Intensive Care

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Background Some unanswered questions persist regarding the effectiveness of corticosteroids for severe coronavirus disease 2019 (COVID-19) patients. We aimed to assess the clinical effect of corticosteroids on intensive care unit (ICU) mortality among mechanically ventilated COVID-19-associated acute respiratory distress syndrome (ARDS) patients. Methods This was a retrospective study of prospectively collected data conducted in 70 ICUs (68 Spanish, one Andorran, one Irish), including mechanically ventilated COVID-19-associated ARDS patients admitted between February 6 and September 20, 2020. Individuals who received corticosteroids for refractory shock were excluded. Patients exposed to corticosteroids at admission were matched with patients without corticosteroids through propensity score matching. Primary outcome was all-cause ICU mortality. Secondary outcomes were to compare in-hospital mortality, ventilator-free days at 28 days, respiratory superinfection and length of stay between patients with corticosteroids and those without corticosteroids. We performed survival analysis accounting for competing risks and subgroup sensitivity analysis. Results We included 1835 mechanically ventilated COVID-19-associated ARDS, of whom 1117 (60.9%) received corticosteroids. After propensity score matching, ICU mortality did not differ between patients treated with corticosteroids and untreated patients (33.8% vs. 30.9%; p = 0.28). In survival analysis, corticosteroid treatment at ICU admission was associated with short-term survival benefit (HR 0.53; 95% CI 0.39–0.72), although beyond the 17th day of admission, this effect switched and there was an increased ICU mortality (long-term HR 1.68; 95% CI 1.16–2.45). The sensitivity analysis reinforced the results. Subgroups of age < 60 years, severe ARDS and corticosteroids plus tocilizumab could have greatest benefit from corticosteroids as short-term decreased ICU mortality without long-term negative effects were observed. Larger length of stay was observed with corticosteroids among non-survivors both in the ICU and in hospital. There were no significant differences for the remaining secondary outcomes. Conclusions Our results suggest that corticosteroid treatment for mechanically ventilated COVID-19-associated ARDS had a biphasic time-dependent effect on ICU mortality. Specific subgroups showed clear effect on improving survival with corticosteroid use. Therefore, further research is required to identify treatment-responsive subgroups among the mechanically ventilated COVID-19-associated ARDS patients.

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“…Other factors related to SARS-CoV-2 infection include the high frequencies of pulmonary emboli and pulmonary infarction, the particular severity and length of ARF that required prolonged mechanical ventilation (12-30 days on average [50]), deep sedation and neuromuscular blockade, and the frequent use of extracorporeal membrane oxygenation [43]. The role of steroid therapy during SARS-CoV-2 infection in the occurrence of bacterial infections is debated [51][52][53][54][55] but has been associated with systemic infections such as invasive aspergillosis [56].…”

Section: Specific Risk In Icumentioning

confidence: 99%

Risk stratification for selecting empiric antibiotherapy during and after COVID-19

Zahar

Timsit

2022

Current Opinion in Infectious Diseases

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Purpose of review SARS-CoV-2 deeply modified the risk of bacterial infection, bacterial resistance, and antibiotic strategies. This review summarized what we have learned. Recent findingsDuring the COVID-19 pandemic, we observed an increase in healthcare-acquired infection and multidrugresistant organism-related infection, triggered by several factors: structural factors, such as increased workload and ongoing outbreaks, underlying illnesses, invasive procedures, and treatment-induced immunosuppression. The two most frequently healthcare-acquired infections described in patients hospitalized with COVID-19 were bloodstream infection, related or not to catheters, health-acquired pneumonia (in ventilated or nonventilated patients). The most frequent species involved in bacteremia were Gram-positive cocci and Gram-negative bacilli in health-acquired pneumonia. The rate of Gram-negative bacilli is particularly high in late-onset ventilator-associated pneumonia, and the specific risk of Pseudomonas aeruginosa-related pneumonia increased when the duration of ventilation was longer than 7 days. A specificity that remains unexplained so far is the increase in enterococci bacteremia.

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Impact of Early Corticosteroids on 60-day Mortality in Critically Ill Patients with COVID-19: A Multicenter Cohort Study of the OUTCOMEREA Network

Cited by 10 publications

References 41 publications

Co-infection and ICU-acquired infection in COVID-19 ICU patients: a secondary analysis of the UNITE-COVID data set

Co-infection and ICU-acquired infection in COVID-19 ICU patients: a secondary analysis of the UNITE-COVID data set

Corticosteroid treatment and mortality in mechanically ventilated COVID-19-associated acute respiratory distress syndrome (ARDS) patients: a multicentre cohort study

Risk stratification for selecting empiric antibiotherapy during and after COVID-19

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