Mesenchymal Stem Cell Therapy for Severe COVID-19 ARDS

Helene Häberle, Harry Magunia, Peter Lang, Henning Gloeckner, Andreas Körner, Michael Koeppen, Tamam Backchoul, Nisar Malek, Rupert Handgretinger, Peter Rosenberger, Valbona Mirakaj, Helene Häberle, Harry Magunia, Peter Lang, Henning Gloeckner, Andreas Körner, Michael Koeppen, Tamam Backchoul, Nisar Malek, Rupert Handgretinger, Peter Rosenberger, Valbona Mirakaj

Abstract

Background: The COVID-19 pandemic reached Germany in spring 2020. No proven treatment for SARS-CoV-2 was available at that time, especially for severe COVID-19-induced ARDS. We determined whether the infusion of mesenchymal stromal cells (MSCs) would help to improve pulmonary function and overall outcome in patients with severe COVID-19 ARDS. We offered MSC infusion as an extended indication to all critically ill COVID-19 patients with a Horovitz index <100. We treated 5 out of 23 patients with severe COVID-19 ARDS with an infusion of MSCs. One million MSCs/kg body weight was infused over 30 minutes, and the process was repeated in 3 patients twice and in 2 patients 3 times.

Result: Four out of 5 MSC-treated patients compared to 50% of control patients (9 out of 18) received ECMO support (80%). The MSC group showed a higher Murray score on admission than control patients, reflecting more severe pulmonary compromise (3.5 ± 0.2 versus 2.8 ± 0.3). MSC infusion was safe and well tolerated. The MSC group had a significantly higher Horovitz score on discharge than the control group. Compared to controls, patients with MSC treatment showed a significantly lower Murray score upon discharge than controls. In the MSC group, 4 out of 5 patients (80%) survived to discharge and exhibited good pulmonary function, whereas only 8 out of 18 patients (45%) in the control group survived to discharge.

Conclusion: MSC infusion is a safe treatment for COVID-19 ARDS that improves pulmonary function and overall outcome in this patient population.

Keywords: ARDS; COVID-19; acute respiratory distress syndrome; inflammation; mesenchymal stem cell therapy; sepsis.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Laboratory values with schematic timeline of the intensive care unit course of MSC-treated patients (blue) and control patients (red). The admission values (ADM) and discharge values (DIS) are compared statistically with nonparametric testing. (A) Total leukocyte counts, (B) neutrophil counts, (C) lymphocyte counts, (D) thrombocyte counts, (E) CRP values in mg/dl during the ICU course, (F) D-Dimer values in mg/dl during, (G) IL-6 serum values, and (H) ferritin values during the ICU course of MSC treated patients and controls. (With n = 5 in the MSC group and n = 18 in the control group, Mann-Whitney U test with *P < 0.05).
Figure 2.
Figure 2.
Schematic graph of ventilation parameters during the intensive care unit course of MSC-treated patients (blue) and control patients (red). The admission values (ADM) and discharge values (DIS) were compared statistically with nonparametric testing. (A) Horovitz index during the ICU course, (B) plateau pressure in cmH2O, (C) compliance in ml/mmHg, and (D) tidal volume in ml (with n = 5 in the MSC group with 4 out of 5 patients extubated at discharge and n = 18 in the control group with n = 5 extubated at discharge, Mann-Whitney U Test with *P < 0.05).
Figure 3.
Figure 3.
Murray score to determine overall pulmonary function during the intensive care unit course of MSC-treated patients (blue) and control patients (red). The admission values (ADM) and discharge values (DIS) were compared statistically with nonparametric testing (with n = 5 in the MSC group with 4 out of 5 patients extubated at discharge and n = 18 in the control group with n = 5 extubated at discharge, Mann-Whitney U test with *P < 0.05).

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