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The mortality attributable to ICU-acquired bloodstream infection (BSI) differs between studies due to statistical methods used for cohort matching. Propensity-score matching has never been used to avoid eventual bias when studying BSI attributable mortality in the ICU. We conducted an observational prospective study over a 4-year period, on patients admitted for at least 48 h in 2 intensive care units. Based on risk factors for death in the ICU and for BSI, each patient with BSI was matched with 3 patients without BSI using propensity-score matching. We performed a competitive risk analysis to study BSI mortality attributable fraction. Of 2464 included patients, 71 (2.9%) had a BSI. Propensity-score matching was highly effective and group characteristics were fully balanced. Crude mortality was 36.6% in patients with BSI and 21.6% in propensity-score matched patients (p=0.018). Attributable mortality of BSI was 2.3% [1.2–4.0] and number needed to harm was 6.7. With Fine and Gray model, a higher risk for death was observed in patients with BSI than in propensity-score matched patients (sub distribution Hazard Ratio (sdHR) = 2.11; 95% CI [1.32–3.37] p = 0.002). Patients with BSI had a higher risk for death and BSI attributable mortality fraction was 2.3%.

The antiviral efficacy of remdesivir against SARS-CoV-2 is still controversial. We aimed to evaluate the clinical efficacy of remdesivir plus standard of care compared with standard of care alone in patients admitted to hospital with COVID-19, with indication of oxygen or ventilator support. DisCoVeRy was a phase 3, open-label, adaptive, multicentre, randomised, controlled trial conducted in 48 sites in Europe (France, Belgium, Austria, Portugal, Luxembourg). Adult patients (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and illness of any duration were eligible if they had clinical evidence of hypoxaemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzymes, severe chronic kidney disease, any contraindication to one of the studied treatments or their use in the 29 days before random assignment, or use of ribavirin, as well as pregnancy or breastfeeding. Participants were randomly assigned (1:1:1:1:1) to receive standard of care alone or in combination with remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, or hydroxychloroquine. Randomisation used computer-generated blocks of various sizes; it was stratified on severity of disease at inclusion and on European administrative region. Remdesivir was administered as 200 mg intravenous infusion on day 1, followed by once daily, 1-h infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale, assessed in the intention-to-treat population. Safety was assessed in the modified intention-to-treat population and was one of the secondary outcomes. This trial is registered with the European Clinical Trials Database, EudraCT2020-000936-23, and ClinicalTrials.gov, NCT04315948. Between March 22, 2020, and Jan 21, 2021, 857 participants were enrolled and randomly assigned to remdesivir plus standard of care (n=429) or standard of care only (n=428). 15 participants were excluded from analysis in the remdesivir group, and ten in the control group. At day 15, the distribution of the WHO ordinal scale was: (1) not hospitalised, no limitations on activities (61 [15%] of 414 in the remdesivir group vs 73 [17%] of 418 in the control group); (2) not hospitalised, limitation on activities (129 [31%] vs 132 [32%]); (3) hospitalised, not requiring supplemental oxygen (50 [12%] vs 29 [7%]); (4) hospitalised, requiring supplemental oxygen (76 [18%] vs 67 [16%]); (5) hospitalised, on non-invasive ventilation or high flow oxygen devices (15 [4%] vs 14 [3%]); (6) hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation (62 [15%] vs 79 [19%]); (7) death (21 [5%] vs 24 [6%]). The difference between treatment groups was not significant (odds ratio 0·98 [95% CI 0·77–1·25]; p=0·85). There was no significant difference in the occurrence of serious adverse events between treatment groups (remdesivir, 135 [33%] of 406 vs control, 130 [31%] of 418; p=0·48). Three deaths (acute respiratory distress syndrome, bacterial infection, and hepatorenal syndrome) were considered related to remdesivir by the investigators, but only one by the sponsor's safety team (hepatorenal syndrome). No clinical benefit was observed from the use of remdesivir in patients who were admitted to hospital for COVID-19, were symptomatic for more than 7 days, and required oxygen support. European Union Commission, French Ministry of Health, Domaine d'intérêt majeur One Health Île-de-France, REACTing, Fonds Erasme-COVID-Université Libre de Bruxelles, Belgian Health Care Knowledge Centre, Austrian Group Medical Tumor, European Regional Development Fund, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation. For the French translation of the abstract see Supplementary Materials section.

Eligible participants were adults (aged ≥18 years) who were admitted to hospital with a positive PCR test for SARS-CoV-2 (<72 h before randomisation) and also had pulmonary rales or crackles with a peripheral oxygen saturation of 94% or less or required supplemental oxygen. Similar to findings from preliminary analyses, participants from the remdesivir group who were not on mechanical ventilation or ECMO when they were randomly assigned to a treatment group (n=692) had a significantly longer time to the composite endpoint of new mechanical ventilation, ECMO, or death in the 29 days following randomisation than did the control group (cumulative incidence in the remdesivir group was 58 [17%] of 343 participants vs 88 [25%] of 349 in the control group; adjusted hazard ratio [HR] 0·63 [95% CI 0·45–0·88]; p=0·010). In non-prespecified analyses, this effect was significant in participants with severe disease when they were randomly assigned to a treatment group (cumulative incidence in the remdesivir group 25 [29%] of 87 vs 47 [50%] of 94 in the control group; unadjusted HR 0·49 [95% CI 0·30–0·80]; p=0·0040) but not in those with moderate disease (33 (13%) of 256 vs 41 (16%) of 255; 0·79 [0·50–1·25]; p=0·31).

We investigated whether baseline levels of biomarkers related to endotheliopathy, thromboinflammation, and fibrosis were associated with clinical outcomes in hospitalized COVID-19 patients. We analyzed the associations between baseline levels of 21 biomarkers and time to hospital discharge and change in NEWS-2 score in patients from DisCoVeRy trial. We fitted multivariate models adjusted for baseline ISARIC 4C score, disease severity, D-dimer values, and treatment regimen. Between March 22 and June 29, 2020, 603 participants were randomized; 454 had a sample collected at baseline and analyzed. The backward selection of multivariate models showed that higher baseline levels of soluble suppressor of tumorigenicity 2 (sST2) and nucleosomes were statistically associated with a lower chance of hospital discharge before day 29 (sST2: aHR 0.24, 95% CI [0.15–0.38], p  < 10 −9 ; nucleosomes: aHR 0.62, 95% CI [0.48–0.81], p  < 10 −3 ). Likewise, higher levels of baseline sST2 were statistically associated with lower changes in the NEWS-2 score between baseline and day 15 (adjusted beta 4.47, 95% CI [2.65–6.28], p  < 10 −5 ). Moreover, we evaluated sST2 involvement in a confirmation cohort (SARCODO study, 103 patients) and found that elevated baseline sST2 levels were significantly associated with lower rates of hospital discharge before day 29 and a higher model performance (AUC at day 29 of 92%) compared to models without sST2. sST2 emerged as an independent predictor of clinical outcomes in two large cohort of hospitalized COVID-19 patients, warranting further investigation to elucidate its role in disease progression and potential as a therapeutic target.