Objectives We aimed to develop and validate a risk score to predict severe respiratory failure (SRF) among patients hospitalized with coronavirus disease-2019 (COVID-19). Methods We performed a multicentre cohort study among hospitalized (>24 hours) patients diagnosed with COVID-19 from 22 February to 3 April 2020, at 11 Italian hospitals. Patients were divided into derivation and validation cohorts according to random sorting of hospitals. SRF was assessed from admission to hospital discharge and was defined as: Sp o 2 <93% with 100% Fi o 2 , respiratory rate >30 breaths/min or respiratory distress. Multivariable logistic regression models were built to identify predictors of SRF, β-coefficients were used to develop a risk score. Trial Registration NCT04316949 . Results We analysed 1113 patients (644 derivation, 469 validation cohort). Mean (±SD) age was 65.7 (±15) years, 704 (63.3%) were male. SRF occurred in 189/644 (29%) and 187/469 (40%) patients in the derivation and validation cohorts, respectively. At multivariate analysis, risk factors for SRF in the derivation cohort assessed at hospitalization were age ≥70 years (OR 2.74; 95% CI 1.66–4.50), obesity (OR 4.62; 95% CI 2.78–7.70), body temperature ≥38°C (OR 1.73; 95% CI 1.30–2.29), respiratory rate ≥22 breaths/min (OR 3.75; 95% CI 2.01–7.01), lymphocytes ≤900 cells/mm 3 (OR 2.69; 95% CI 1.60–4.51), creatinine ≥1 mg/dL (OR 2.38; 95% CI 1.59–3.56), C-reactive protein ≥10 mg/dL (OR 5.91; 95% CI 4.88–7.17) and lactate dehydrogenase ≥350 IU/L (OR 2.39; 95% CI 1.11–5.11). Assigning points to each variable, an individual risk score (PREDI-CO score) was obtained. Area under the receiver-operator curve was 0.89 (0.86–0.92). At a score of >3, sensitivity, specificity, and positive and negative predictive values were 71.6% (65%–79%), 89.1% (86%–92%), 74% (67%–80%) and 89% (85%–91%), respectively. PREDI-CO score showed similar prognostic ability in the validation cohort: area under the receiver-operator curve 0.85 (0.81–0.88). At a score of >3, sensitivity, specificity, and positive and negative predictive values were 80% (73%–85%), 76% (70%–81%), 69% (60%–74%) and 85% (80%–89%), respectively. Conclusion PREDI-CO score can be useful to allocate resources and prioritize treatments during the COVID-19 pandemic.

Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

Objectives To assess the efficacy of corticosteroids in patients with coronavirus disease 2019 (COVID-19) Methods Multicenter observational study from February 22 through June 30, 2020. We included consecutive adult patients with severe COVID-19 defined as respiratory rate ≥30 breath per minute, oxygen saturation ≤93% on ambient air or arterial partial pressure of oxygen to fraction of inspired oxygen ≤300 mmHg. We excluded patients treated with other immunomodulant drugs, receiving low dose of corticosteroids and those receiving corticosteroids after 72h from admission. The primary endpoint was 30-day mortality form hospital admission. The main exposure variable was corticosteroid therapy at dosage of ≥0.5 mg/kg of prednisone equivalents. It was introduced as binomial covariate in a logistic regression model for primary endpoint and inverse probability of treatment weighting using the propensity score. Results Of 1717 patients with COVID-19 evaluated, 513 patients were included in the study; of these 170 (33%) were treated with corticosteroids. During the hospitalization 166 (34%) patients reached the primary outcome [60/170 (35%) in the corticosteroid group and 106/343 (31%) in the non-corticosteroid group]. At multivariable analysis corticosteroid treatment was not associated with lower 30-day mortality rate [aOR 0.59 (0.20-1.74), p=0.33]. After inverse probability of treatment weighting, corticosteroids were not associated to lower 30-day mortality [average treatment effect 0.05 (95% -0.02 to 0.09), p=0.12]. However, subgroup analysis revealed that in patients with PO 2 /FiO 2 < 200 mmHg at admission [135 patients, 52 (38%) treated with corticosteroids] corticosteroid treatment was associated to a lower risk of 30-day mortality [23/52 (44%) vs 45/83 (54%), aOR 0.20 (95%CI 0.04 to 0.90), p=0.036]. Conclusion Our study shows that the effect of corticosteroid treatment on mortality might be limited to critically ill COVID-19 patients.