Conquering the cytokine storm in COVID-19-induced ARDS using placenta-derived decidua stromal cells

Abstract

Acute respiratory distress syndrome (ARDS) is the most common cause of death in COVID-19 patients. The cytokine storm is the main driver of the severity and magnitude of ARDS. Placenta-derived decidua stromal cells (DSCs) have a stronger immunosuppressive effect than other sources of mesenchymal stromal cells. Safety and efficacy study included 10 patients with a median age of 50 (range 14-68) years with COVID-19-induced ARDS. DSCs were administered 1-2 times at a dose of 1 × 10⁶ /kg. End points were safety and efficacy by survival, oxygenation and effects on levels of cytokines. Oxygenation levels increased from a median of 80.5% (range 69-88) to 95% (range 78-99) (p = 0.012), and pulmonary infiltrates disappeared in all patients. Levels of IL-6 decreased from a median of 69.3 (range 35.0-253.4) to 11 (range 4.0-38.3) pg/ml (p = 0.018), and CRP decreased from 69 (range 5-169) to 6 (range 2-31) mg/ml (p = 0.028). Two patients died, one of a myocardial infarction and the other of multiple organ failure, diagnosed before the DSC therapy. The other patients recovered and left the intensive care unit (ICU) within a median of 6 (range 3-12) days. DSC therapy is safe and capable of improving oxygenation, decreasing inflammatory cytokine level and clearing pulmonary infiltrates in patients with COVID-19.

Keywords: COVID-19; cytokine storm; decidua stromal cells; intensive care unit; survival.

FIGURE 1

Phenotypic analysis of decidua stromal cells (DSCs) by flow cytometry. The coloured graphs show the expression of the different cell surface markers (filled areas under the curve) compared to unstained DSC controls (white areas under the curve). The percentages represent the size of each population as a proportion of the whole population

FIGURE 2

Computed tomography (CT) scan images of the lungs in patients with COVID‐19 infection before and after decidua stromal cells (DSC) therapy. (A) Lung CT scan of patient 9902, 2 days before and 4 days after DSCs treatment (1 day after the second DSC dose). For more information, refer to the text. (B) Lung CT scan of patient 9903, 2 days before and 9 days after DSC treatment (4 days after the second DSC dose). For more information, refer to the text. For a better overview of the changes, live CT scan images are available as Supplementary Files

FIGURE 3

Changes in the levels of cytokines and inflammatory mediators following decidua stromal cells (DSC) treatment. (A) Median levels of IL‐6 before and after the first and second DSC infusions (PV = 0.028, N = 7). (B) Median levels of CRP before and after the first and second DSC infusions (PV = 0.028, N = 7). (C) Median levels of G‐CSF before and after the first and second DSC infusions (N = 7). (D) Median levels of CCL‐2 before and after the first and second DSC infusions (N = 7). In the graphs, ‘base’ means 1 day before DSC therapy; ‘after DSC 1’ means 1 day after the first DSC infusion, and ‘after DSC 2’ means 1 day after the last DSC infusion or on the day of discharge

FIGURE 4

Changes in median blood oxygen levels in patients (N = 8) at admission, before and after each decidua stromal cells (DSCs) infusion, and at the time of discharge