Background In the early phase of the pandemic, some guidelines recommended the use of corticosteroids for critically ill patients with COVID‐19, whereas others recommended against the use despite lack of firm evidence of either benefit or harm. In the COVID STEROID trial, we aimed to assess the effects of low‐dose hydrocortisone on patient‐centred outcomes in adults with COVID‐19 and severe hypoxia. Methods In this multicentre, parallel‐group, placebo‐controlled, blinded, centrally randomised, stratified clinical trial, we randomly assigned adults with confirmed COVID‐19 and severe hypoxia (use of mechanical ventilation or supplementary oxygen with a flow of at least 10 L/min) to either hydrocortisone (200 mg/day) versus a matching placebo for 7 days or until hospital discharge. The primary outcome was the number of days alive without life support at day 28 after randomisation. Results The trial was terminated early when 30 out of 1,000 participants had been enrolled because of external evidence indicating benefit from corticosteroids in severe COVID‐19. At day 28, the median number of days alive without life support in the hydrocortisone versus placebo group were 7 versus 10 (adjusted mean difference: ‐1.1 days, 95% CI ‐9.5 to 7.3, p = 0.79); mortality was 6/16 versus 2/14; and the number of serious adverse reactions 1/16 versus 0/14. Conclusions In this trial of adults with COVID‐19 and severe hypoxia, we were unable to provide precise estimates of the benefits and harms of hydrocortisone as compared with placebo as only 3% of the planned sample size were enrolled.

Background Rapid recognition and antibiotic treatment, preferably preceded by blood cultures (BCs), is a mainstay in sepsis therapy. The objective of this investigation was to determine if pre‐hospital BCs were feasible and drawn with an acceptably low level of contamination and to investigate whether pre‐hospital antibiotics were administered on correct indications. Methods We performed a register‐based study in a pre‐hospital physician‐manned mobile emergency care unit (MECU) operating in a mixed urban/rural area in Denmark. All patients who received pre‐hospital antibiotics by the MECU from November 2013 to October 2018 were reviewed. Outcome measures were characterisation of microbial findings and subsequent in‐hospital confirmation of the pre‐hospital indication for antibiotics. Results One‐hundred‐and‐nineteen patients received antibiotics pre‐hospitally. Six were excluded. One‐hundred‐and‐thirteen patients were included in the study. BCs were drawn in 107 of the 113 patients (94.7% [88.8%‐98.0%]). We found a true pathogen of sepsis in 29 (27.1% [19.0%‐36.6%]) of these 107 patients. Nine (8.4% [3.9%‐15.4%]) patients had contaminated pre‐hospital BCs. Forty‐nine of all patients (36.3% [27.4%‐45.9%]) had causative pathogens in either their BCs or other samples confirming the pre‐hospital tentative diagnosis. Eighty‐two (72.6% [63.4%‐80.5%]) patients received antibiotic therapy in‐hospitally, while 27 (23.9% [16.4%‐32.8%]) were assigned an in‐hospital diagnosis not associated with infection. Four (3.5% [1.0%‐8.8%]) patients died in hospital before a diagnosis was established. Conclusions Pre‐hospital administration of antibiotics preceded by BCs is feasible, although with somewhat high blood culture contamination rates. Antibiotics are administered on reasonable indications.

Background Superinfection following viral infection is a known complication, which may lead to longer hospitalisation and worse outcome. Empirical antibiotic therapy may prevent bacterial superinfections, but may also lead to overuse, adverse effects and development of resistant pathogens. Knowledge about the incidence of superinfections in intensive care unit (ICU) patients with severe Coronavirus Disease 2019 (COVID‐19) is limited. Methods We will conduct a nationwide cohort study comparing the incidence of superinfections in patients with severe COVID‐19 admitted to the ICU compared with ICU patients with influenza A/B in Denmark. We will include approximately 1000 patients in each group from the time period of October 1 st , 2014 to April 30 th , 2019 and from March 10 th , 2020 to March 1 st , 2021 for patients with influenza and COVID‐19, respectively. The primary outcome is any superinfection within 90 days of admission to the ICU. We will use logistic regression analysis comparing COVID‐19 with influenza A/B after adjustment for relevant predefined confounders. Secondarily, we will use unadjusted and adjusted logistic regression analyses to assess six potential risk factors (sex, age, cancer (including haematological), immunosuppression, use of life support on day 1 in the ICU) for superinfections, and compare outcomes in patients with COVID‐19 with/without superinfections, and present descriptive data regarding the superinfections. Conclusion This study will provide important knowledge about superinfections in ICU patients with severe COVID‐19.