Mesenchymal stem cells in the treatment of severe COVID-19

• Published in: Translational medicine communications Vol. 6; no. 1; pp. 1 - 16
• Main Authors: Kesari, Santosh, Kasper, Gregory C., Verkh, Lev, Hammond, Terese C., Matal, Marla L., Hammerling, Jay W., Tankovich, Nikolai, Lim, Adrianus P., Zhao, Kevin H., Juarez, Tiffany, Redfern, Roberta E., Gill, Jaya M., Nomura, Natsuko, Hiemer, Audrey, Heng, Annie, Shoemaker, Jessica
• Format: Journal Article
• Language: English
• Published: London BioMed Central 09.08.2021; BMC
• Subjects: Coronaviruses; COVID-19; Cytokine storm; Disease; Influenza; Laboratories; Patients; Pneumonia; Respiratory distress syndrome; Stem cells; Ventilators; United States > US
• ISSN: 2396-832X; 2396-832X
• DOI: 10.1186/s41231-021-00095-0

MSCs are used in the treatment of a range of immune-mediated inflammatory diseases such as lupus erythematous and graft versus host disease [2, 3]. [...]MSCs reduced mortality in H5N1 influenza and resulted in improved survival in those with H7N9 influenza strain who developed ARDS [1]. All patients (n = 14) Emergency use (n = 9) Expanded use (n = 5) Median age – years (range) 58.5 (30 – 84) 64 (56 – 84) 38.0 (30 – 59) Female sex – n (%) 6 (42.9) 4 (44.4) 2 (40) Comorbid conditions  Cardiovascular disease – n (%) 1 (7.1) 1 (11.1) 0 (0)  COPD – n (%) 4 (28.6) 4 (44.4) 0 (0)  Hypertension – n (%) 7 (50) 7 (77.8) 0 (0)  Obesity – n (%) 8 (57.1) 3 (33.3) 5 (100)  Other pulmonary disease – n (%) 6 (42.9) 6 (66.6) 0 (0)  Type II diabetes – n (%) 3 (21.4) 2 (22.2) 1 (20) COVID-19 Severity on admission  Severe – n (%) 5 (35.7) 5 (55.6) 0 (0)  Critically severe – n (%) 9 (64.3) 4 (44.4) 5 (100) Days of admission prior to treatment with MSCs – median (range) 10 (2 – 77) 4 (2 – 12) 41 (13 – 77) Days between MSC treatments – median (range) a 5 (2 – 8) 3 (2 – 3) 7 (6 – 8) Failed or concurrent therapies  Antibiotics 14 (100) 9 (100) 5 (100)  Antiviral 5 (35.7) 1 (11.1) 4 (80)  Convalescent serum 6 (42.9) 1 (11.1) 5 (100)  Hydroxychloroquine 8 (57.1) 5 (55.6) 3 (60)  Interleukin-6 inhibitor 6 (42.9) 1 (11.1) 5 (100)  Steroids 10 (71.4) 8 (88.9) 2 (40) Oxygen therapy required  Mechanical ventilation 10 (71.4) 5 (55.6) 5 (100)  ECMO 5 (35.7) 0 (0) 5 (100) Pneumonia 13 (92.9) 8 (88.9) 5 (100) Concurrent bacterial pneumonia 7 (50) 2 (22.2) 5 (100) ARDS 9 (64.3) 4 (44.4) 5 (100) LOS post-treatment 15 (2 – 50) 13 (2 – 50) 17 (15 – 25) Total length of stay days b 31.5 (5 – 98) 17 (5 – 63) 71 (45 – 98) Survival – post treatment with MSCs  7 days 13 (92.9) 8 (88.9) 5 (100)  14 days 12 (85.7) 7 (77.8) 5 (100)  21 days 12 (85.7) 7 (77.8) 5 (100)  30 days 9 (64.3) 7 (77.8) 2 (40) 1. a 3 of 8 Emergency Use patients were treated with one bolus of 100 × 106 cells 2. b includes 2 patients admitted at time of writing Following treatment with MSCs, four of five mechanically ventilated emergency use cases were extubated, exhibiting marked improvement on radiographic examination (Fig. 1). Infiltrates reduced on day 4 following MSC treatment (L) While this was not a clinical trial designed and powered for comparisons, our data suggest that those who received MSCs earlier in their clinical course of disease may have appreciated more benefit; it is possible that earlier treatment may help prevent the cytokine storm, rather than attempting to reverse it.