Abstract
BackgroundSome 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.MethodsThis 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.ResultsWe 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.ConclusionsOur 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.
Highlights
Some unanswered questions persist regarding the effectiveness of corticosteroids for severe coro‐ navirus disease 2019 (COVID-19) patients
Larger length of stay was observed with corticosteroids among non-survivors both in the intensive care unit (ICU) and in hospital
Our results suggest that corticosteroid treatment for mechanically ventilated COVID-19-associated acute respiratory distress syndrome (ARDS) had a biphasic time-dependent effect on ICU mortality
Summary
Some unanswered questions persist regarding the effectiveness of corticosteroids for severe coro‐ navirus 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. It has been more than a year since the devastating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak occurred, which emerged in Wuhan (China) on December 2019, and the global health issue is still a concern to resolve. The clinical presentation ranges from asymptomatic or mild-to-severe pneumonia in which the most critical cases develop life-threatening acute respiratory distress syndrome (ARDS), requiring admission to the intensive care unit (ICU) with high rates of invasive mechanical ventilation and mortality [2]. Clinical effectiveness of corticosteroid treatment in COVID-19 patients with ARDS is still limited and conflicted by the results from some meta-analysis [7, 8] and observational data [9,10,11]
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