Coronavirus disease 2019 (COVID-19) may result in a life-threatening condition due to a hyperactive immune reaction to severe acute respiratory syndrome-coronavirus-2 infection, for which no effective treatment is available. Based on the potent immunomodulatory properties of mesenchymal stromal cells (MSCs), a growing number of trials are ongoing. This prompted us to carry out a thorough immunological study in a patient treated with umbilical cord-derived MSCs and admitted to the Intensive Care Unit for COVID-19-related pneumonia. The exploratory analyses were assessed on both peripheral blood and bronchoalveolar fluid lavage samples at baseline and after cellular infusion by means of single-cell RNA sequencing, flow cytometry, ELISA, and functional assays. Remarkably, a normalization of circulating T lymphocytes count paralleled by a reduction of inflammatory myeloid cells, and a decrease in serum levels of pro-inflammatory cytokines, mostly of interleukin-6 and tumor necrosis factor-α, were observed. In addition, a drop of plasma levels of those chemokines essential for neutrophil recruitment became evident that paralleled the decrease of lung-infiltrating inflammatory neutrophils. Finally, circulating monocytes and low-density gradient neutrophils acquired immunosuppressive function. This scenario was accompanied by an amelioration of respiratory, renal, inflammatory, and pro-thrombotic indexes. Our results provide the first immunological data possibly related to the use of umbilical cord-derived MSCs in severe COVID-19 context. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-021-02376-9.
【저자키워드】 COVID-19, Cytokines, Mesenchymal stromal cells, scRNA-seq, Inflammatory response, 【초록키워드】 Treatment, Coronavirus disease 2019, Trial, severe COVID-19, Pneumonia, neutrophil, Infection, intensive care unit, myeloid cells, interleukin-6, MSCs, flow cytometry, ELISA, chemokine, Single-cell RNA sequencing, Peripheral blood, Patient, plasma, pro-inflammatory cytokines, cellular, Inflammatory, MSC, immunosuppressive, stromal cell, reduction, tumor necrosis factor-α, supplementary material, Serum level, Exploratory analysis, life-threatening, T lymphocyte, low-density, circulating, neutrophil recruitment, renal, immune reaction, immunological, effective, decrease, bronchoalveolar, assays, addition, treated, functional, accompanied, baseline, circulating monocyte, immunomodulatory property, inflammatory neutrophils, pro-thrombotic, umbilical, were assessed, 【제목키워드】 Severe COVID-19 pneumonia, stromal cell, immune modulatory effect, umbilical,