Superinfections in critically ill COVID-19 patients - an association with Dexamethasone? (preprint)

BacgroundSuper-infections in COVID-19 patients with acute respiratory distress syndrome (ARDS) on mechanical ventilation were initially reported to be rare. Little is known of their incidence after dexamethasone was introduced as standard care. We aimed to determine the incidence and characteristics of superinfections in mechanically ventilated COVID-19 patients during the course of the COVID-19 pandemic, and explore the possible impact of the introduction of dexamethasone as standard therapy. MethodsIn this national, multi-center, observational, retrospective study we included patients ≥ 18 years admitted from March 1 st 2020 to January 31 st 2021 with polymerase chain reaction (PCR)-confirmed SARSCoV-2 infection treated with invasive mechanical ventilation. Data was collected from electronic health records. Patient characteristics, clinical findings, microbiology, length of stay and 90-day survival were examined with backwards stepwise multiple regression. Results155 patients (115 men, mean age 62 years, range 26-84 years) were included. 73 patients (47%) had a total of 101 superinfections where pneumonia dominated (70%). Superinfections were more commonly observed in patients receiving dexamethasone (67% vs 30%, p<0.0001), and in patients with pre-existing autoimmune disease (18% vs 5%, p<0.01). Invasive fungal infections were reported exclusively in dexamethasone-treated patients [9/72 (13%) vs 0/83 (0%), p<0.0001]. There was no difference in 90-day survival between patients with and patients without superinfections (64% versus 73%, p=0.238). In multiple regression analysis, superinfection was associated with dexamethasone use [OR 5.35 (2.62–11.35), p<0.001], pre-existing autoimmune disease [OR 4.90 (1.50–19.4), p=0.008] and higher lymphocyte count at the time of admission [OR 2.31 (1.23–4.86), p=0.009]. ConclusionIn critically ill COVID-19 patients receiving invasive ventilation, introduction of dexamethasone as standard of care was strongly and independently associated with superinfections. A focus on this complication is warranted when studying alternative anti-inflammatory therapy.

National Early Warning Score 2 (NEWS2) on admission predicts severe disease and in-hospital mortality from Covid-19 - A prospective cohort study (preprint)

Background: There is a need for validated clinical risk scores to identify patients at risk of severe disease and to guide decision-making during the covid-19 pandemic. The National Early Warning Score 2 (NEWS2) is widely used in emergency medicine, but so far, no studies have evaluated its use in patients with covid-19. We aimed to study the performance of NEWS2 and compare commonly used clinical risk stratification tools at admission to predict risk of severe disease and in-hospital mortality in patients with covid-19. Methods: This was a prospective cohort study in a public non-university general hospital in the Oslo area, Norway, including a cohort of all 66 patients hospitalised with confirmed SARS-CoV-2 infection from the start of the pandemic; 13 who died during hospital stay and 53 who were discharged alive. Data were collected consecutively from March 9 th to April 27 th 2020. The main outcome was the ability of the NEWS2 score and other clinical risk scores at emergency department admission to predict severe disease and in-hospital mortality in covid-19 patients. We calculated sensitivity and specificity with 95% confidence intervals (CIs) for NEWS2 scores ≥5 and ≥6, quick Sequential Organ Failure Assessment (qSOFA) score ≥2, ≥2 Systemic Inflammatory Response Syndrome (SIRS) criteria, and CRB-65 score ≥2. Areas under the curve (AUCs) for the clinical risk scores were compared using DeLong’s test. Results: In total, 66 patients (mean age 67.9 years) were included. Of these, 23% developed severe disease. In-hospital mortality was 20%. Tachypnoea, hypoxemia and confusion at admission were more common in patients developing severe disease. A NEWS2 score ≥6 at admission predicted severe disease with 80.0% sensitivity and 84.3% specificity (Area Under the Curve (AUC) 0.822, 95% confidence interval (CI) 0.690-0.953). NEWS2 was superior to qSOFA score ≥2 (AUC 0.624, 95% CI 0.446-0.810, p<0.05) and other clinical risk scores for this purpose. Conclusion: NEWS2 score at hospital admission predicted severe disease and in-hospital mortality, and was superior to other widely used clinical risk scores in patients with covid-19.