Impact of Mesenchymal Stromal/stem Cell Infusions on Circulating Inflammatory Biomarkers in COVID-19 Patients: Analysis of a Phase I-IIa Trial.

Background- SARS-CoV-2 infection triggers respiratory inflammation with potentially fatal systemic effects. Mesenchymal stromal/stem cells (MSCs) are promising for treating severe COVID- 19 due to their anti-inflammatory and regenerative capacities. This study investigates the effects of allogeneic MSCs in severe COVID-19 pneumonia. Methods- In the phase I/IIa RESCAT trial (May 2021–Feb 2022), patients with severe COVID-19 pneumonia received two intravenous MSC infusions and were compared to a control group (CTRL). To assess cytokine and biomarker responses, the MSC group was matched 1:2 with standard care patients (mCTRL) by age, gender, BMI, and PaO2/FiO2 (Nov 2020–Feb 2021). Random-effects linear regression evaluated cytokine and biomarker trends over time between MSC and control groups. Results- 17 patients (MSC=5, CTRL=2, mCTRL=10) were analyzed. Two MSC infusions were feasible and safe, with all patients discharged on average 15±3.7 days post-second infusion. While IL1RA and IL18 levels significantly increased in CTRL-mCTRL patients (p=0.044 and p=0.032), MSC treatment averted these rises, showing a distinct trajectory, particularly for IL1RA. MSC treatment also reduced IL6 levels compared to CTRL-mCTRL, while both groups showed similar reductions in Long pentraxin. Furthermore, MSC infusions prevented the neurofilament light chain surge observed in CTRL patients. Conclusions- MSC in COVID-19 patients resulted safe and feasible, effectively modulating inflammatory cytokines, in particular mitigating brain damage related biomarker, suggesting both reduced inflammation and a potential neurological protection.