Human umbilical cord-derived mesenchymal stem cell therapy in patients with COVID-19: a phase 1 clinical trial

Abstract

No effective drug treatments are available for coronavirus disease 2019 (COVID-19). Host-directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage, death, or long-term functional disability in survivors require clinical evaluation. We performed a parallel assigned controlled, non-randomized, phase 1 clinical trial to evaluate the safety of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) infusions in the treatment of patients with moderate and severe COVID-19 pulmonary disease. The study enrolled 18 hospitalized patients with COVID-19 (n = 9 for each group). The treatment group received three cycles of intravenous infusion of UC-MSCs (3 × 10 7 cells per infusion) on days 0, 3, and 6. Both groups received standard COVID-treatment regimens. Adverse events, duration of clinical symptoms, laboratory parameters, length of hospitalization, serial chest computed tomography (CT) images, the PaO 2 /FiO 2 ratio, dynamics of cytokines, and IgG and IgM anti-SARS-CoV-2 antibodies were analyzed. No serious UC-MSCs infusion-associated adverse events were observed. Two patients receiving UC-MSCs developed transient facial flushing and fever, and one patient developed transient hypoxia at 12 h post UC-MSCs transfusion. Mechanical ventilation was required in one patient in the treatment group compared with four in the control group. All patients recovered and were discharged. Our data show that intravenous UC-MSCs infusion in patients with moderate and severe COVID-19 is safe and well tolerated. Phase 2/3 randomized, controlled, double-blinded trials with long-term follow-up are needed to evaluate the therapeutic use of UC-MSCs to reduce deaths and improve long-term treatment outcomes in patients with serious COVID-19.

Transplantation of Mesenchymal Stem Cells: A Potential Adjuvant Therapy for COVID-19

“…Due to the small sample size, there was no comparative analysis between the two groups, but the patients in the MSCs group displayed a reduction of serum IL-6. Moreover, this trial demonstrated that transplantation of MSCs in patients with COVID-19 was safe and no serious adverse events were reported (Meng et al, 2020). In addition, a case report has described the clinical application of human umbilical cord-derived MSCs in a patient with severe COVID-19 pneumonia, who was intravenous injected with 1 × 10 6 cells/kg.…”

SARS-CoV-2 and Malayan pangolin coronavirus infect human endoderm, ectoderm and induced lung progenitor cells

“…Surprisingly, the pangolin coronavirus of GX_P2V could not only infect human mature somatic cells 1 , but also infect the hESCs, endoderm, ectoderm, hAFECs and hLPCs, indicating the possibility of the cross-species transmission and potential danger of coronavirus from animals. However, both viruses could not infect mesoderm, even though it expresses viral recptor of ACE2 and TMPRSS2, indicating the potential inhibitory activity of mesoderm to these coronaviruses, which may explain why mesenchymal stem cells could be used as a therapy tool for COVID-19 treatment 15 . The potential consequence of SARS-CoV-2 and animal coronavirus such as GX_P2V infection in hESCs, germ layer and induced progenitors should be closely monitored.…”

Overview of current adipose-derived stem cell (ADSCs) processing involved in therapeutic advancements: flow chart and regulation updates before and after COVID-19

“…Autologous and allogenic MSC therapy has emerged as inhibiting of the immune system and thus treating COVID-19 pneumonia [ 13 , 14 , 21 ]. Assessing safety and efficacy of UC-MSCs in treating the pneumonia associated to the viral infection represents the major objective of these clinical trials [ 160 – 163 ]. UC-MSCs are also used in treating pneumonia in patients infected with coronavirus [ 164 , 165 ].…”

“…First published results with infused umbilical cord MSCs (UC-MSCs) to critically ill COVID-19 patients present an improved therapeutic outcome [ 156 , 162 , 163 ]. Other strategies consisted of using ACE2 − UC-MSCs leading to an improved pulmonary functional activity and absence of SARS-CoV-2 nucleic acid with more benefit to elderly patients [ 148 ].…”