Glucocorticoids improve severe or critical COVID-19 by activating ACE2 and reducing IL-6 levels

Abstract

COVID-19 is a public health emergency that has rapidly spread to over 200 countries and regions, and no effective treatment has been established to date. Severe and critical cases have been associated with higher mortality due to acute respiratory distress syndrome (ARDS) and cytokine storm. Based on the novelty and recent emergence of COVID-19, no effective treatment regimen has been identified, thus prompting clinicians to engage in drug repurposing to address the immediate therapeutic need. This study focused on the molecular target angiotensin-converting enzyme 2 (ACE2) of SARS-CoV-2 and screened a group of ACE2 agonists by bioinformatics. Glucocorticoids are a type of ACE2 activator. We verified the efficacy of nine chemicals on regulating ACE2 expression in human GES-1, an upper digestive tract epithelial cell line, and THP-1, a human monocyte cell line, and found that several glucocorticoids imparted activating effects on ACE2 in both cell lines. The drugs triciribine and kinetin riboside activate ACE2 expression or inhibit IL-6 production in macrophages to some extent. In addition, we compared the efficacies of several glucocorticoids. Hydrocortisone showed the strongest effect on ACE2 activation, followed by prednisolone, dexamethasone, and methylprednisolone. We retrospectively analyzed the therapeutic efficacy of nine severe or critical patients from a cohort of 90 COVID-19 cases, who received medium to small doses of glucocorticoids from our integrated medical team in Wuhan. Seven out of nine patients revealed significant improvement in clinical parameters and chest CT images. This study provides experimental and clinical evidence that medium-to-low-dose glucocorticoids may play a protective role in the respiratory and digestive systems by activating ACE2 and suppressing cytokine storm.

Temporal Changes in Clinical Practice with COVID-19 Hospitalized Patients: Potential Explanations for Better In-Hospital Outcomes

“…One key intervention is mechanical ventilation, initially thought to be best started early with more severe COVID-19 respiratory finding, notably hypoxemia. Over time, informal reports note less mechanical ventilation use; potential explanations for lower rates of COVID-19 mechanical ventilation and less mortality include: (i) changing demographics of patients; 5 (ii) more judicious use of starting and using mechanical ventilation; 6 (iii) more frequent use of anticoagulants; 7,8 and steroids; [9][10][11][12] (iv) changing prominent disease manifestations of patients; 13 (v) seasonal effects of temperature and humidity variation; 14 and (vi) potential changes in viral infectivity or pathogenicity. 15,16 There have been temporal changes in COVID-19 testing in addition to no national testing strategy.…”

Case Report: Emergency CABG Following Failure of PTCA in a COVID-19 Patient

“…It is also mandatory the need to have strict management protocols for these patients who undergo cardiac surgery in cardiopulmonary bypass due to the elevated risk of “cytokine storm” and post-operative pulmonary impairment. Systemic corticosteroids may have a potential pivotal role in the management of these patients; as reported by Xiang et al ( 22 ) they improve severe COVID-19 by reducing IL-6 levels and activating ACE2. Interesting findings from a randomized control trial evidenced the effectiveness of corticosteroids during CPB to reduced IL-6 expression ( p < 0.001) until 48 h after surgery compared to controls and extracorporeal hemadsorption ( 23 ).…”

Cuadro Clínico Del Covid-19

“…Esta respuesta debe estar en equilibrio entre la eliminación del virus y evitar el daño pulmonar inmunomediado, que es en donde los corticoides juegan un rol antiinflamatorio, inhibiendo múltiples citoquinas 27 . Además, se ha evidenciado que los corticoides, como efecto de familia, aumentan la transcripción de la ECA2 28 , que al ser usada por el SARS-CoV-2 para infectar a las células, se depleta promoviendo un exceso de angiotensina lo que aumenta el daño pulmonar en fases tardías.…”