Date of Admission during COVID-19 Pandemic Impacted Patient Outcomes in Addition to the Higher Efficacy of Tocilizumab Plus High-Dose Corticosteroid Therapy Compared to Tocilizumab Alone.

BACKGROUND: The evidence for the efficacy of glucocorticoids combined with tocilizumab (TCZ) in COVID-19 comes from observational studies or subgroup analysis. Our aim was to compare outcomes between hospitalized COVID-19 patients who received high-dose corticosteroid pulse therapy and TCZ and those who received TCZ. METHODS: A retrospective single-center study was performed on consecutive hospitalized patients with severe COVID-19 between 1 March and 23 April 2020. Patients treated with either TCZ (400-600 mg, one to two doses) and methylprednisolone pulses (MPD-TCZ group) or TCZ alone were analyzed for the occurrence of a combined endpoint of death and need for invasive mechanical ventilation during admission. The independence of both treatment groups was tested using machine learning classifiers, and relevant variables that were potentially different between the groups were measured through a mean decrease accuracy algorithm. RESULTS: An earlier date of admission was significantly associated with worse outcomes regardless of treatment type. Twenty patients died (27.0%) in the TCZ group, and 33 (44.6%) died or required intubation (n = 74), whereas in the MPD-TCZ group, 15 (11.0%) patients died and 29 (21.3%) patients reached the combined endpoint (n = 136; p = 0.006 and p < 0.001, respectively). Machine learning methodology using a random forest classifier confirmed significant differences between the treatment groups. CONCLUSIONS: MPD and TCZ improved outcomes (death and invasive mechanical ventilation) among hospitalized COVID-19 patients, but confounding variables such as the date of admission during the COVID-19 pandemic should be considered in observational studies.

Low molecular weight heparin is useful in adult COVID-19 inpatients. Experience during the first Spanish wave: observational study.

BACKGROUND: The intensity of the thromboprophylaxis needed as a potential factor for preventing inpatient mortality due to coronavirus disease-19 (COVID-19) remains unclear. OBJECTIVE: To explore the association between anticoagulation intensity and COVID-19 survival. DESIGN AND SETTING: Retrospective observational study in a tertiary-level hospital in Spain. METHODS: Low-molecular-weight heparin (LMWH) status was ascertained based on prescription at admission. To control for immortal time bias, anticoagulant use was analyzed as a time-dependent variable. RESULTS: 690 patients were included (median age, 72 years). LMWH was administered to 615 patients, starting from hospital admission (89.1%). 410 (66.7%) received prophylactic-dose LMWH; 120 (19.5%), therapeutic-dose LMWH; and another 85 (13.8%) who presented respiratory failure, high D-dimer levels (> 3 mg/l) and non-worsening of inflammation markers received prophylaxis of intermediate-dose LMWH. The overall inpatient-mortality rate was 38.5%. The anticoagulant nonuser group presented higher mortality risk than each of the following groups: any LMWH users (HR 2.1; 95% CI: 1.40-3.15); the prophylactic-dose heparin group (HR 2.39; 95% CI, 1.57-3.64); and the users of heparin dose according to biomarkers (HR 6.52; 95% CI, 2.95-14.41). 3.4% of the patients experienced major hemorrhage. 2.8% of the patients developed an episode of thromboembolism. CONCLUSIONS: This observational study showed that LMWH administered at the time of admission was associated with lower mortality among unselected adult COVID-19 inpatients. The magnitude of the benefit may have been greatest for the intermediate-dose subgroup. Randomized controlled trials to assess the benefit of heparin within different therapeutic regimes for COVID-19 patients are required.