Comparison of the efficacy of equivalent doses of dexamethasone, methylprednisolone, and hydrocortisone for treatment of COVID-19-related acute respiratory distress syndrome: a prospective three-arm randomized clinical trial.

BACKGROUND: This prospective controlled clinical trial aimed to compare the efficacy of methylprednisolone, dexamethasone, and hydrocortisone at equivalent doses in patients with severe COVID-19. METHODS: In total, 106 patients with mild to moderate COVID-19-related acute respiratory distress syndrome (ARDS) were randomized to receive either dexamethasone (6 mg once a day), methylprednisolone (16 mg twice a day), or hydrocortisone (50 mg thrice a day) for up to 10 days. All participants received a standard of care for COVID-19. The primary and secondary efficacy outcomes included all-cause 28-day mortality, clinical status on day 28 assessed using the World Health Organization (WHO) eight-category ordinal clinical scale, number of patients requiring mechanical ventilation and intensive care unit (ICU) care, number of ventilator-free days, length of hospital and ICU stay, change in PaO2:FiO2 ratios during the first 5 days after treatment, and incidence of serious adverse events. P-values below 0.008 based on Bonferroni's multiple-testing correction method were considered statistically significant. RESULTS: According to the obtained results, there was a trend toward more favorable clinical outcomes in terms of needing mechanical ventilation and ICU care, number of ventilator-free days, change in PaO2:FiO2 ratios during the first 5 days after treatment, clinical status score at day 28, length of ICU and hospital stay, and overall 28-day mortality in patients receiving dexamethasone compared to those receiving methylprednisolone or hydrocortisone; however, likely due to the study's small sample size, the difference between groups reached a significant level only in the case of clinical status score on day 28 (p-value = 0.003). There was no significant difference in the incidence of serious adverse events between the study groups. CONCLUSION: Based on the results, severe cases of COVID-19 treated with dexamethasone might have a better clinical status at 28-day follow-up compared to methylprednisolone and hydrocortisone at an equivalent dose. Larger multicenter trials are required to confirm our findings.

Is there any association between plasma lipid profile and severity of COVID-19?

BACKGROUND: COVID-19 is an infectious disease which caused a pandemic with many diseases and fatalities. This new variant of coronavirus called SARS-CoV-2 and is primarily characterized by respiratory symptoms. There are some data indicating that LDL-cholesterol (LDL-C) as well as HDL-cholesterol (HDL-C) levels are inversely correlated to disease severity and could act as a predictor for disease progression and unfavorable prognosis. However, the results of some other studies do not confirm this. This current study aimed to provide an answer to this question. METHODS: This prospective, single-center study analyzed 367 confirmed COVID-19 patients to find whether there are any differences in plasma lipoproteins between survivors and non-survivors patients or between the patients with a "duration of ≤10 days intensive unit care (ICU) stay" and patients with a "duration of >10 days ICU stay". RESULTS: No association between any lipid/lipoprotein parameter and the severity of COVID-19 could be found but survivors and non-survivors did differ concerning total cholesterol and LDL-C levels. CONCLUSION: Multivariate cox regression analysis could not prove any association between lipids/lipoproteins and severe events in COVID-19 patients. Significantly less non-survivors with COVID-19 were taking atorvastatin than survivors which is consistent with the majority of previous findings.

A pilot study on intravenous N-Acetylcysteine treatment in patients with mild-to-moderate COVID19-associated acute respiratory distress syndrome.

BACKGROUND: We designed this single-centre clinical trial to assess the potential benefits of N-Acetylcysteine (NAC) in patients with COVID19-associated acute respiratory distress syndrome (ARDS). METHODS: Ninety-two patients with mild-to-moderate COVID19-associated ARDS were allocated to the placebo (45-cases) or NAC groups (47-cases). Besides standard-of-care treatment, the patients received either intravenous NAC at a dose of 40 mg/kg/day or the placebo for three consecutive days. The efficacy outcomes were overall mortality over 28-day, clinical status on day 28, based on the WHO Master Protocol, the proportion of patients requiring mechanical ventilation, changes in ARDS-severity (based on the PaO2/FiO2 ratio), and Sequential Organ Failure Assessment (SOFA) scores 48 and 96 h after intervention, RESULTS: No differences were found in the 28-day mortality rate between the two groups (25.5% vs. 31.1% in the NAC and placebo groups, respectively). Although the distribution of the clinical status at day 28 shifted towards better outcomes in the NAC-treated group, it did not reach a statistical significance level (p value = 0.83). Similar results were achieved in terms of the proportion of patients who required invasive ventilator support (38.3% vs. 44.4%), the number of ventilator-free days (17.4 vs. 16.6), and median time of ICU and hospital stay. Results regarding the change in PaO2/FiO2 ratio and SOFA scores also showed no significant differences between the groups. CONCLUSIONS: Our pilot study did not support the potential benefits of intravenous NAC in treating patients with COVID-19-associated ARDS. More studies are needed to determine which COVID-19 patients benefit from the NAC administration. TRIAL REGISTRATION: The trial was registered at Clinicaltrials.gov (identifier code: IRCT20120215009014N355). Registration date: 2020-05-18.