Case Report: Successful Treatment of Five Critically Ill Coronavirus Disease 2019 Patients Using Combination Therapy With Etoposide and Corticosteroids

Abstract

Acute respiratory distress syndrome (ARDS) is the leading cause of mortality in hospitalized patients with coronavirus disease 2019 (COVID-19) because of limited effective therapies. During infection, the accumulation and activation of macrophages and monocytes in the lungs induce inflammatory mediators and contribute to tissue injury, leading to ARDS. However, therapeutic strategies that directly target activated macrophage and monocytes have not been reported. Combination treatment with etoposide (a cytotoxic agent) and a corticosteroid has been widely used for treating hemophagocytic lymphohistiocytosis characterized by the systemic activation of macrophages with overwhelming inflammation. Herein, we present five cases of COVID-19-associated ARDS treated with etoposide and corticosteroids. Three of the five patients were over 65 years of age and had various underlying diseases, including multiple myeloma. Four patients required invasive mechanical ventilation (MV), and one patient refused to be placed on MV due to underlying diseases. All patients were pre-treated with antiviral and/or other anti-inflammatory agents, but their condition deteriorated and hyperinflammation was noted. All five patients responded well to treatment and had an immediate response, as reflected by improvement in their respiratory condition and inflammatory marker levels and rapid resolution of fever after etoposide administration; however, some patients required a second dose of etoposide and longer course of steroids. All patients recovered, and there were no severe adverse events related to the drugs. Following successful treatment in these five patients, we plan to conduct a clinical trial to evaluate the efficacy and safety of combination therapy with etoposide and corticosteroid for treating COVID-19 patients in Japan.

Patients with Hemophagocytic Lymphohistiocytosis Who Need Intensive Care Can Be Successfully Rescued by Timely Using Etoposide-Based HLH Regimens

“… 34 , 35 Aoyagi et al have improved respiratory status and inflammatory marker levels in ARDS patients with etoposide and corticosteroids. 36 In addition, Vigneron et al have observed a reduction in non-PLT SOFA (npSOFA) in HLH patients treated with etoposide. 37 Therefore, we chose the etoposide-based regimen for critically ill patients.…”

COVID-19 Associated Cardiovascular Disease—Risks, Prevention and Management: Heart at Risk Due to COVID-19

“…Given the multifaceted symptomology of COVID-19, ranging from patients with asymptomatic infection to those with severe disease burden requiring mechanical ventilation, the overall treatment strategy for COVID-19 may vary across patient populations. For patients with a mild illness, treatment primarily consists of the isolation and care of symptoms [ 76 ]. For those with a more severe disease course, the infection may cause severe viral pneumonia.…”

“…This task is accomplished by supplemental oxygenation and mechanical lung-protective ventilation to prevent the development of ARDS [ 77 ]. The use of systemic corticosteroids in patients with confirmed COVID-19 pneumonia who require oxygen therapy due to hypoxia decreases mortality [ 76 , 77 , 78 , 79 , 80 , 81 ]. Antibiotics are not routinely started because bacterial coinfection with COVID-19 is rare; however, a broad-spectrum antibiotic regimen is used if a superimposed infection is suspected [ 82 , 83 , 84 ].…”