Background: Passive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19 for which evidence from controlled clinical trials is lacking. Methods: We conducted a multi-center, randomized clinical trial in patients hospitalized for COVID-19. All patients received standard of care treatment, including off-label use of marketed medicines, and were randomized 1:1 to receive one dose (250-300 mL) of CP from donors with IgG anti-SARS-CoV-2. The primary endpoint was the proportion of patients in categories 5, 6 or 7 of the COVID-19 ordinal scale at day 15. Results: The trial was stopped after first interim analysis due to the fall in recruitment related to pandemic control. With 81 patients randomized, there were no patients progressing to mechanical ventilation or death among the 38 patients assigned to receive plasma (0%) versus 6 out of 43 patients (14%) progressing in control arm. Mortality rates were 0% vs 9.3% at days 15 and 29 for the active and control groups, respectively. No significant differences were found in secondary endpoints. At inclusion, patients had a median time of 8 days (IQR, 6-9) of symptoms and 49,4% of them were positive for anti-SARS-CoV-2 IgG antibodies. Conclusions: Convalescent plasma could be superior to standard of care in avoiding progression to mechanical ventilation or death in hospitalized patients with COVID-19. The strong dependence of results on a limited number of events in the control group prevents drawing firm conclusions about CP efficacy from this trial. (Funded by Instituto de Salud Carlos III; NCT04345523).

Background: Evidence to support the use of steroids in COVID-19 pneumonia is lacking. We aim to determine the impact of steroid use in COVID-19 pneumonia in-hospital mortality. Patients and Methods: We performed a single-center retrospective cohort study in a University hospital in Madrid, Spain, during March 2020. To determine the role of steroids in in-hospital mortality, patients admitted with SARS-CoV-2 pneumonia and treated with steroids were compared to patients not treated with steroids, adjusting by a propensity-score for steroid treatment. Survival times were compared using log-rank test. Different steroid regimens were compared, and adjusted with a second propensity score. Results: During the study period, 463 out of 848 hospitalized patients with COVID19 pneumonia fulfilled inclusion criteria. Among them, 396 (46.7%) patients were treated with steroids and 67 patients were not. Global mortality was 15.1%. Median time to steroid treatment from symptom onset was 10 days (IQR 8-13). In-hospital mortality was lower in patients treated with steroids than in controls (13.9% [55/396] versus 23.9% [16/67], HR 0.51 [0.27-0.96], p= 0.044). Steroid treatment reduced mortality by 41.8% relative to no steroid treatment (RRR 0,42 [0.048- 0.65). Initial treatment with 1 mg/kg/day of methylprednisolone versus steroid pulses was not associated with in-hospital mortality (13.5% [42/310] versus 15.1% [13/86], OR 0.880 [0.449-1.726], p=0.710). Conclusions: Our results show that survival of patients with SARS-CoV2 pneumonia is higher in patients treated with glucocorticoids than in those not treated. In-hospital mortality was not different between initial regimens of 1 mg/kg/day of methylprednisolone and glucocorticoid pulses.

for the ConPlas-19 Study Group* *Complete list of the ConPlas-19 study group provided in the Supplement.

Objective: We aim to determine the impact of steroid use in COVID-19 pneumonia in-hospital mortality. Design: We performed a single-centre retrospective cohort study. Setting: A University hospital in Madrid, Spain, during March 2020. Participants: Patients admitted with SARS-CoV-2 pneumonia. Exposures: Patients treated with steroids were compared to patients not treated with steroids. A propensity-score for steroid treatment was developed. Different steroid regimens were also compared, and adjusted with a second propensity score. Main Outcomes and Measures: To determine the role of steroids in in-hospital mortality, univariable and multivariable analyses were performed, and adjusted including the propensity score as a covariate. Survival times were compared using a log-rank test. Results: During the study period, 463 out of 848 hospitalized patients with COVID19 pneumonia fulfilled inclusion criteria. Among them, 396 (46.7%) consecutive patients were treated with steroids and 67 patients were assigned to the control cohort. Global mortality was 15.1%. Median time to steroid treatment from symptom onset was 10 days (IQR 8 to13). In-hospital mortality was lower in patients treated with steroids than in controls (13.9% [55/396] versus 23.9% [16/67], OR 0.51 [0.27 to 0.96], p= 0.044). Steroid treatment reduced mortality by 41.8% relative to no steroid treatment (RRR 0,42 [0.048 to 0.65). Initial treatment with 1 mg/kg/day of methylprednisolone (or equivalent) versus steroid pulses was not associated with in-hospital mortality (13.5% [42/310] versus 15.1% [13/86], OR 0.880 [0.449-1.726], p=0.710). Conclusions: Our results show that survival of patients with SARS-CoV2 pneumonia is higher in patients treated with glucocorticoids than in those not treated. In-hospital mortality was not different between initial regimens of 1 mg/kg/day of methylprednisolone or equivalent and glucocorticoid pulses. These results support the use of glucocorticoids in SARS-CoV2 infection.

ORTHOUNION is a multicentre, open, comparative, three-arm, randomized clinical trial (EudraCT number 2015-000431-32) to compare the efficacy, at one and two years, of autologous human bone marrow-derived expanded mesenchymal stromal cell (hBM-MSC) treatments versus iliac crest autograft (ICA) to enhance bone healing in patients with diaphyseal and/or metaphysodiaphyseal fracture (femur, tibia, and humerus) status of atrophic or oligotrophic nonunion (more than 9 months after the acute fracture, including recalcitrant cases after failed treatments). The primary objective is to determine if the treatment with hBM-MSCs combined with biomaterial is superior to ICA in obtaining bone healing. If confirmed, a secondary objective is set to determine if the dose of 100 × 106 hBM-MSCs is noninferior to that of 200 × 106 hBM-MSCs. The participants (n = 108) will be randomly assigned to either the experimental low dose (n = 36), the experimental high dose (n = 36), or the comparator arm (n = 36) using a central randomization service. The trial will be conducted in 20 clinical centres in Spain, France, Germany, and Italy under the same clinical protocol. The confirmation of superiority for the proposed ATMP in nonunions may foster the future of bone regenerative medicine in this indication. On the contrary, absence of superiority may underline its limitations in clinical use.