Objective To analyze the effects of a short course of methyl-prednisolone pulses (MP) during the second week of disease (week-2) in patients with severe coronavirus disease 2019 (COVID-19) pneumonia. Methods Comparative observational study using data collected from routine care at Hospital Universitario Cruces, Barakaldo, Bizkaia, Spain in patients with COVID-19 pneumonia. We compared patients who received week-2-MP (125-250 mg/d x3) with those who did not, with the end-points time to death and time to death or endotracheal intubation. Results We included 242 patients with COVID-19 pneumonia and elevated inflammatory markers at admission. Sixty-one patients (25%) received week-2-MP. Twenty-two patients (9%) died and 31 (12.8%) suffered death or intubation. The adjusted HRs for death and death or intubation for patients in the week-2-MP group were 0.35 (95%CI 0.11 to 1.06, p = 0.064) and 0.33 (95%CI 0.13 to 0.84, p = 0.020), respectively. These differences were specifically seen in the subcohort of patients with a SpO2/FiO2 at day 7 lower than 353 (adjusted HR 0.31,

OBJECTIVE: To analyze the effects of a short course of methyl-prednisolone pulses (MP) during the second week of disease (week-2) on the clinical course of patients with severe coronavirus disease 2019 (COVID-19) pneumonia. DESIGN: Comparative observational study using data collected from routine care. SETTING: Hospital Universitario Cruces, a tertiary level University hospital at Barakaldo, Bizkaia, Spain. PARTICIPANTS: All patients with COVID-19 pneumonia admitted between 1st March and 30th April 2020 to the services of Infectious Diseases and Internal Medicine. INTERVENTIONS: Treatment with week-2-MP (125-250 mg/d for 3 consecutive days with no subsequent tapering) vs. standard of care. MAIN OUTCOMES MEASURES: Time to death and time to death or endotracheal intubation. RESULTS: Two hundred and forty-two patients with confirmed COVID-19 pneumonia and elevated inflammatory markers at admission were included in the study. Sixty-one patients (25%) received week-2-MP. Twenty-two patients (9%) died during the study period. Thirty-one patients (12.8%) suffered death or intubation. The adjusted HR for death was 0.35 (95%CI 0.11 to 1.06, p= 0.064) for patients in the week-2-MP group. The adjusted HR for death or intubation week-2-MP was 0.33 (95%CI 0.13 to 0.84, p=0.020) for patients in the week-2-MP group. These differences were seen in the subcohort of patients with a SaO2/FiO2 at day 7 lower than the median of the whole population: HR 0.31, 95% CI 0.08 to 1.12, p=0.073 and HR 0.34, 95%CI 0.12 to 0.94, p=0.038, respectively, but not in patients with higher SaO2/FiO2. Other predictors of the final outcomes were arterial hypertension, SaO2/FiO2, high-risk CURB65 scores and the use of non-pulse glucocorticoids. Non-pulse glucocorticoids were a predictor of infections (OR 4.72, 95%CI 1.90 to 11.80, p<0.001), while week-2-MP were not (OR 1.04, 95%CI 0.40 to 2.70, p=0.938). CONCLUSIONS: Week-2-MP are effective in improving the prognosis of patients with COVID-19 pneumonia with features of inflammatory activity and respiratory deterioration entering the second week of disease. The recognition of this high-risk population should prompt early use of MP at this point. REGISTRATION: This study has been registered in the EU PAS Register with the number EUPAS36287.

Background This study was designed to evaluate if patients with high risk for severe COVID-19 would benefit from treatment with TDF/FTC followed by baricitinib in case of hypoxemia and systemic inflammation. Methods PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥ 2 comorbidities or older than 60 years conducted between 10 October 2020 and 23 September 2021. In the first randomization patients received TDF/FTC or not TDF/FTC. In the second randomization patients with room-air O2 saturation &lt;95% and at least one increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in the number of cases and a mortality rate substantially lower than expected EudraCT registration number: 2020-001156-18. Results Of the 355 included participants 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% CI 0.52-5.91; p= 0.379); it was 0.42 (95% CI 0.11-1.59; p= 0.201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI 0.66-1.40; p = 0.774); it was 0.90 (95%CI 0.61-1.33; p = 0.687) for those treated with baricitinib. Conclusions Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials.