ABSTRACT
Background: COVID-19 carries a high risk of vascular thrombosis. This joint analysis of two randomized-controlled trials (RCTs) aims to assess the safety and efficacy of enoxaparin at therapeutic dose compared to prophylactic dose in people hospitalized with COVID-19. Method(s): A joint analysis of two RCTs, COVID-19 HD (NCT044082359) and EMOS-COVID (NCT04646655), was performed. Both studies enrolled inpatients with COVID-19- associated respiratory compromise (as identified by respiratory rate >=25 breaths/min or arterial oxygen saturation <=93% at rest or PaO2/FiO2 <=300 mmHg for COVID-19 HD and by PaO2/FiO2 <=250 mmHg for EMOS-COVID) and/or coagulopathy (D-dimer > 2000 ng/ml for both RCTs or sepsis-Induced coagulopathy score >4 for COVIDHD). In both RCTs patients were randomly assigned to two arms: enoxaparin at prophylactic dose (standard 4.000 IU;in the EMOS-COVID 6000 IU if body weight >100 kg) and at therapeutic dose (70 U/Kg every 12 h). The primary efficacy endpoint of the joint analysis was clinical worsening, defined as the occurrence of at least one among: in-hospital death;acute myocardial infarction;symptomatic arterial or venous thromboembolism;need of either Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) in patients who were in standard oxygen therapy at randomization;need for IMV in any patient. The primary outcome was assessed as time-to-event, described with hazard ratio (HR) and with Kaplan-Meier survival estimate. The primary safety endpoint was major bleeding for both trials and for the joint analysis. Result(s): COVID-19 HD enrolled 142 people between July 2, 2020 and February 15, 2022, while EMOS-COVID enrolled 141 people from July 27, 2020 to June 5, 2021, resulting in 283 patients included in this joint analysis. Two-hundredseven (73.1%) were males, with a mean age of 61.1 years (SD +/-10.7), a mean BMI of 29.7 kg/m2 (SD +/-5.0), and 115 (40.6%) were on NIV or Cpap at randomization, with no significant difference between the study groups. 21/139 people in the high dose group reached the primary endpoint compared to 32/144 in the prophylactic group (HR 0.63, 95%CI 0.36 to 1.10). Figure 1 shows the Kaplan- Meier survival estimates of clinical worsening. No major bleeding was observed during the study time. Conclusion(s): The results of this joint analysis did not highlight significant differences in clinical worsening between COVID-19 patients that received enoxaparin at therapeutic compared to prophylactic dose. (Figure Presented).
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.