ABSTRACT
Background: Pulse glucocorticoid therapy (> 250 mg of prednisone equivalent per day for 1 or a few days) is used in many immuno-inflammatory diseases for its quick and strong anti-inflammatory effect in emergency situations. It was used during in Severe Acute Respiratory Syndrome epidemics with no consistent data regarding its benefits. The efficacy and safety of this therapy associated to dexamethasone in coronavirus disease 2019 (Covid-19) pneumonia are unclear. Methods: We conducted a double-blind, randomized, placebo-controlled trial in hospitalized patients with COVID19-pneumonia. The study population included patients hospitalized for recent-onset Covid-19 pneumonia requiring supplemental oxygen in any delivery mode, except invasive mechanical ventilation, with PaO2/FiO2 between 100 and 300, and a C-reactive protein greater than 5 mg/dl. Patients were randomly assigned to receive 1 gram of methylprednisolone for 3 consecutive days or placebo in addition to standard dexamethasone. The primary outcome was the duration of the patient hospitalization, calculated as the time interval between randomization and hospital discharge without the need of supplementary oxygen. All-cause mortality, survival free from invasive ventilation and safety were also evaluated. Written informed consent was obtained from each patient or from the patient's legally authorized representative if the patient was unable to provide consent. Results: A total of 304 patients underwent randomization in 19 Italian sites between December 21, 2020, and March 10, 2021. Three patients retired the consent to the study one day after randomization, leaving 301 patients eligible for intention to treat analyses. 112 of 151 (74.2%) patients in the pulse methylprednisolone arm and 111 of 150 (74.0%) patients in the placebo arm were discharged from hospital without oxygen (p = 0.528) within 28 days from randomization. We did not observe any significant differences between pulse methylprednisolone and placebo arms in terms of admission to Intensive Care Unit with orotracheal intubation or death (19.9% versus 16.0% respectively;hazard ratio, 1.27;95%CI, 0.74-2.16), or in terms of overall mortality (9.3% versus 11.3% respectively;hazard ratio, 0.82;95%CI, 0.40-1.66). Serious adverse events occurred in 9 patients (6.0%) in the methylprednisolone pulse group and in 12 patients (8.0%) in the placebo group. Conclusion: Methylprednisolone pulse therapy in addition to dexamethasone was not of benefit in patients with COVID-19 pneumonia.
ABSTRACT
Background: Muscle and fat mass loss as a consequence of protein catabolism and prolonged immobilization is frequent in critically ill patients. Post-COVID acute sarcopenia may be due also to inflammaging for the strong inflammatory reaction. The study aims were to describe changes in chest CT body composition parameters from baseline to follow-up CT scan in severe COVID-19 survivors, and to evaluate the impact of COVID-19 inflammatory burden on these changes. Methods: Baseline (t0), 2-3 months (t1) and 6-7 months (t2) follow-up CT scan of severe COVID-19 pneumonia survivors were retrospectively reviewed to measure pectoralis muscle area (PMA) and density (PMD), liver-to-spleen ratio (LSR), and total, visceral, and intermuscular adipose tissue areas (TAT, VAT and IMAT) at T7-T8 vertebrae. C-reactive protein (CRP) curve integral was used to describe COVID-19 inflammatory burden, and its impact on body composition changes was evaluated in multivariable linear regression models adjusted for age, sex, and baseline TAT (index of general adiposity). Results: At follow-up a decrease in mean PMA and in all mean body fat areas was registered, faster from t0 to t1, and slower from t1 to t2, with the exception of PMD, which increased (i.e. intramuscular fat decreased) only from t1 to t2 (Table). Mean VAT decrease was more conspicuous than mean TAT decrease. In models adjusted for age, sex, and baseline TAT, increasing CRP integral was significantly associated with higher PMA reduction (p=0,017 for delta t2-t0) and lower PMD increase (p=0.01 for delta t2-t0), higher LSR increase (i.e. higher steatosis decrease) (p<0.0001 for delta t1-t0, n.s. for delta t2-t0), and higher VAT decrease (p=0.035 for delta t2-t0), but not with TAT decrease. These associations were stronger in patients with higher VAT and lower LSR at baseline. Conclusion: Muscle and fat loss after COVID-19 is faster in the first months, but slowly continues till 6-7 months. Fat loss is more apparent in visceral compartments. Inflammatory burden is associated with the degree of muscle and visceral/liver fat loss.
ABSTRACT
Objective: To estimate the effect of tocilizumab or glucocorticoids in preventing death and intubation in patients hospitalized with SARS-CoV-2 pneumonia.Methods: This was a retrospective cohort study enrolling all consecutive patients hospitalized at Reggio Emilia AUSL between February the 11th and April 14th 2020 for severe COVID19 and treated with tocilizumab or glucocorticoids (at least 80 mg/day of methylprednisolone or equivalent for at least 3 days).The primary outcome was death within 30 days from the start of the considered therapies. The secondary outcome was a composite outcome of death and/or intubation. All patients have been followed-up until May 19th 2020, with a follow-up of at least 30 days for every patient. To reduce confounding due to potential non-comparability of the two groups, those receiving tocilizumab and those receiving glucocorticoids, a propensity score was calculated as the inverse probability weighting of receiving treatment conditional on the baseline covariates.Results and conclusion: Therapy with tocilizumab alone was associated with a reduction of deaths (OR 0.49, 95% CI 0.21-1.17) and of the composite outcome death/intubation (OR 0.35, 95% CI 0.13-0.90) compared to glucocorticoids alone. Nevertheless, this result should be cautiously interpreted due to a potential prescription bias.(c) 2021 Sociedade Brasileira de Infectologia. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
ABSTRACT
Objectives: To identify predictors of clinical improvement and intubation/death in tocilizumab-treated severe COVID19, focusing on IL6 and CRP longitudinal monitoring.