No abstract

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).

Background and aims Despite anticoagulation, usually with heparin, mortality for thromboembolic events in COVID-19 remains high. Clinical efficacy of heparin is due to its interaction with antithrombin (AT) that may be decreased in COVID-19. Therefore, we correlated AT levels with outcomes of COVID-19. Methods and results We recruited 49 consecutive patients hospitalized for COVID-19. AT levels were significantly lower in 16 non-survivors than in 33 survivors (72.2 ± 23.4 versus 94.6 ± 19.5%; p = 0.0010). A multivariate Cox regression analysis showed that low AT (levels below 80%) was a predictor of mortality (HR:3.97; 95%CI:1.38 to 11.43; p = 0.0103). BMI was the only variable that showed a significant difference between patients with low and those with normal AT levels (32.9 ± 7.9 versus 27.5 ± 5.9%; p = 0.0104). AT levels were significantly lower in obese patients than in subjects with normal weight or overweight (77.9 ± 26.9 versus 91.4 ± 26.9 versus 91.4 ± 17.1%; p = 0.025). An inverse correlation between AT levels and BMI was documented (r:-0.33; p = 0.0179). Conclusions Our data first suggest that AT is strongly associated with mortality in COVID-19. In addition, AT may be the link between obesity and a poorer prognosis in patients with COVID-19. Other studies should confirm whether AT may become a prognostic marker and a therapeutic target in COVID-19.

No abstract

Coronavirus disease 2019 (COVID-19) is characterized by a procoagulant state that can lead to fatal thromboembolic events. Several studies have documented a high prevalence of lupus anticoagulant that may at least partially explain the procoagulant profile of COVID-19. However, the association between lupus anticoagulant and thrombotic complications in COVID-19 is controversial and no study has specifically evaluated the impact of lupus anticoagulant on mortality. The aim of our study was to investigate the association between lupus anticoagulant and mortality in a large group of 192 consecutive patients hospitalized for COVID-19. Lupus anticoagulant was found in 95 patients (49.5%). No difference in the percentage of patients with lupus anticoagulant was observed between 130 survivors and 62 non-survivors (47.7 versus 53,2%; p = 0.4745). When the combined outcome of death or need for mechanical ventilation in survivors was taken into account, the difference in the prevalence of patients with lupus anticoagulant between the patients with the combined outcome (n = 76) and survivors who did not require mechanical ventilation (n = 116) was not significant (52.6% versus 47.4%; p = 0.4806). In multivariate analysis predictors of mortality or need for mechanical ventilation in survivors were obesity, low oxygen saturation and elevated troponin levels measured on admission. In conclusion, our study did not show any association of lupus anticoagulant with mortality and with need for mechanical ventilation in survivors. The role of obesity, low SaO2 and elevated troponin levels as predictors of a worse prognosis in patients hospitalized for COVID-19 was confirmed.