RATIONALE: Mesenchymal stromal cells (MSCs) may modulate inflammation, promoting repair in COVID-19-related Acute Respiratory Distress Syndrome (ARDS).

OBJECTIVES: We investigated safety and efficacy of ORBCEL-C (CD362-enriched, umbilical cord-derived MSCs) in COVID-related ARDS.

METHODS: This multicentre, randomised, double-blind, allocation concealed, placebo-controlled trial (NCT03042143) randomised patients with moderate-to-severe COVID-related ARDS to receive ORBCEL-C (400million cells) or placebo (Plasma-Lyte148).

MEASUREMENTS: The primary safety and efficacy outcomes were incidence of serious adverse events and oxygenation index at day 7 respectively. Secondary outcomes included respiratory compliance, driving pressure, PaO2/FiO2 ratio and SOFA score. Clinical outcomes relating to duration of ventilation, length of intensive care unit and hospital stays, and mortality were collected. Long-term follow up included diagnosis of interstitial lung disease at 1 year, and significant medical events and mortality at 2 years. Transcriptomic analysis was performed on whole blood at day 0, 4 and 7.

MAIN RESULTS: 60 participants were recruited (final analysis n=30 ORBCEL-C, n=29 placebo: 1 in placebo group withdrew consent). 6 serious adverse events occurred in the ORBCEL-C and 3 in the placebo group, RR 2.9(0.6-13.2)p=0.25. Day 7 mean[SD] oxygenation index did not differ (ORBCEL-C 98.357.2], placebo 96.667.3). There were no differences in secondary surrogate outcomes, nor mortality at day 28, day 90, 1 or 2 years. There was no difference in prevalence of interstitial lung disease at 1year nor significant medical events up to 2 years. ORBCEL-C modulated the peripheral blood transcriptome.

CONCLUSION: ORBCEL-C MSCs were safe in moderate-to-severe COVID-related ARDS, but did not improve surrogates of pulmonary organ dysfunction. Clinical trial registration available at www.

CLINICALTRIALS: gov, ID: NCT03042143. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).


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Cite as

Gorman, E., Rynne, J., Gardiner, H., Rostron, A., Bannard-Smith, J., Bentley, A., Brealey, D., Campbell, C., Curley, G., Clarke, M., Dushianthan, A., Hopkins, P., Jackson, C., Kefala, K., Krasnodembskaya, A., Laffey, J., McDowell, C., McFarland, M., McFerran, J., McGuigan, P., Perkins, G., Silversides, J., Smythe, J., Thompson, J., Tunnicliffe, W., Welters, I., Amado-Rodríguez, L., Albaiceta, G., Williams, B., Shankar-Hari, M., O'Kane, C. & McAuley, D. 2023, 'Repair of Acute Respiratory Distress Syndrome in COVID-19 by Stromal Cells (REALIST-COVID Trial): A Multicentre, Randomised, Controlled Trial', American Journal of Respiratory and Critical Care Medicine, 21, article no: 462. https://doi.org/10.1186/s13063-020-04416-w

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Last updated: 26 October 2023
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