Effectiveness and safety profile of mesenchymal stem cell secretome as a treatment for severe cases of COVID-19: a randomized controlled trial

Abstract

Background:  Mesenchymal stem cells (MSCs) are known to have immunomodulatory, anti-inflammatory, anti-apoptotic, and angiogenesis effects that are useful for relieving inflammation, recovery, and protection of lung tissues in COVID-19 patients. Secretome, a secretory product of MSCs, has several advantages over MSCs. We conducted a study to investigate secretomes’ effectiveness and safety profile as a treatment for severe COVID-19.  Methods:  A double-blind, multicenter, randomized, placebo-controlled trial was conducted between February 2021 and July 2021 in three top COVID-19 referral hospitals in the Greater Jakarta area, Indonesia. Eligible subjects (n=40) were randomized in a 1:1 ratio to an intervention group (n=20) and a control group (n=20). The primary outcome of this study was the changes in inflammatory markers and the ratio of inflammatory to anti-inflammatory markers. The secondary outcomes of this study included clinical outcome, laboratory outcome, radiological outcome, RT-PCR result conversion, and safety profile of MSC secretome. Results:  Our analysis showed that on the 14th day after placebo administration, IL-6 level in the control group was significantly increased [4.110 (2.403–12.820) at baseline to 13.320 (2.958–33.285) on the 14th day after intervention, p=0.017]. The IL-6/IL-10 ratio in the control group was significantly increased (p=0.036) on the 14th day after placebo administration. We also found that most of the subjects who received placebo had high levels of IL-6 and ferritin (p=0.043) on the seventh day after the intervention. However, we found no significant differences in inflammatory marker levels on the seventh day and 14th day after intervention between both groups. There was no adverse event reported. There were no significant differences in the laboratory outcome, radiology outcome, RT-PCR result conversion, and safety profiles between both groups. Conclusions:  MSC secretome can control inflammation in patients with severe COVID-19 and has a good safety profile. MSC secretome is a promising treatment modality for severe COVID-19.