High-dose corticosteroid pulse therapy increases the survival rate in COVID-19 patients at risk of hyper-inflammatory response

Abstract

Objective Test whether high dose corticosteroid pulse therapy (HDCPT) with either methylprednisolone or dexamethasone is associated with increased survival in COVID-19 patients at risk of hyper-inflammatory response. Provide some initial diagnostic criteria using laboratory markers to stratify these patients. Methods This is a prospective observational study, 318 met the inclusion criteria. 64 patients (20.1%) were treated with HDCPT by using at least 1.5mg/kg/24h of methylprednisolone or dexamethasone equivalent. A multivariate Cox regression (controlling for co-morbidities and other therapies) was carried out to determine whether HDCPT (among other interventions) was associated with decreased mortality. We also carried out a 30-day time course analysis of laboratory markers between survivors and non-survivors, to identify potential markers for patient stratification. Results HDCPT showed a statistically significant decrease in mortality (HR = 0.087 [95% CI 0.021–0.36]; P < 0.001). 30-day time course analysis of laboratory marker tests showed marked differences in pro-inflammatory markers between survivors and non-survivors. As diagnostic criteria to define the patients at risk of developing a COVID-19 hyper-inflammatory response, we propose the following parameters (IL-6 > = 40 pg/ml, and/or two of the following: C-reactive protein > = 100 mg/L, D-dimer > = 1000 ng/ml, ferritin > = 500 ng/ml and lactate dehydrogenase > = 300 U/L). Conclusions HDCPT can be an effective intervention to increase COVID-19 survival rates in patients at risk of developing a COVID-19 hyper-inflammatory response, laboratory marker tests can be used to stratify these patients who should be given HDCPT. This study is not a randomized clinical trial (RCT). Future RCTs should be carried out to confirm the efficacy of HDCPT to increase the survival rates of COVID-19.

High-Dose Methylprednisolone Pulses for 3 Days vs. Low-Dose Dexamethasone for 10 Days in Severe, Non-Critical COVID-19: A Retrospective Propensity Score Matched Analysis

“…However, a PSM analysis was not performed and the final duration of CS was also not specified. Furthermore, López-Zúñiga et al retrospectively compared high dose CS (>1.5 mg/kg/day of MP or DXM equivalent) vs. low dose (<1.5 mg/kg/day of MP or DXM equivalent), showing a reduction in mortality with the use of high-dose CS pulse therapy (HR = 0.087; 0.02–0.36; p < 0.001) [ 30 ]. However, despite the notable sample size (299 severe-critical COVID-19 patients), PSM analysis was not performed, nor did it specify treatment duration or inflammatory parameters at admission.…”

High-dose dexamethasone treatment for COVID-19 severe acute respiratory distress syndrome: a retrospective study

“…In spite of these positive results, recently some papers came out questioning the positive effects of high-dose glucocorticoids, either dexamethasone or methylprednisolone [34][35][36]. However, other studies supported the beneficial effects of an immediate blunting of hyperinflammation using high-dose glucocorticoids in terms of increased survival [37][38][39].…”

Is butyrate a natural alternative to dexamethasone in the management of CoVID-19?

“…Intravenous dexamethasone treatment for CoVID-19 patients along with standard care significantly decreases the number of ventilator dependent days over 28 days 11 . High dose pulse therapy of dexamethasone increased the survival rate in CoVID-19 patients presented with hyperinflammation 126 . However, dexamethasone, a broad spectrum immunosuppressant, inhibits lymphocytes function and prevents macrophage mediated removal of apoptotic cells, which leads to reduced viral shedding and increases subsequent viremia in mild to moderately ill CoVID-19 patients 124 , 127 , 128 .…”