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

Fanping Meng,Tianjun Jiang,Xing Fan,Limin Liu,Ming Shi,Yuanyuan Li,Peng Zhao,Junliang Fu,Tao Yang,Markus Maeurer,Xin Yuan,Chao Zhang,Ruonan Xu,Alimuddin Zumla,Jiyuan Zhang ,Dawei Zhang,Chun‐Bao Zhou ,Lei Huang,Yan‐Mei Jiao ,Zhe Xu,Siyu Wang,Jin‐Wen Song ,Lei Shi,Fusheng Wang

doi:10.1038/s41392-020-00286-5

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 × 107 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 PaO2/FiO2 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.

Highlights

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)infection in humans has led to an ongoing pandemic of coronavirus disease 2019 (COVID-19) worldwide
One patient (C1) in the control group, and two patients (T5 and T9) in the umbilical cord-derived mesenchymal stem cells (UC-Mesenchymal stem cells (MSCs)) treatment group were viral RNA negative at enrollment, the others were positive for plasma viral RNA
The duration from first symptom onset to hospital admission in the UC-MSCs treatment group ranged from day 3 to 15; in the control group it ranged from day 4 to 11

Summary

Introduction

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)infection in humans has led to an ongoing pandemic of coronavirus disease 2019 (COVID-19) worldwide. COVID-19 causes a spectrum of clinical illness from mild, moderate, to severe or critical disease.[1] As of 6 July 2020, there have been 532,340 deaths from COVID-19 out 11,327,790 cases reported to the World Health Organization.[2] While. COVID-19 predominantly affects the respiratory tract, it is a multisystem disease, and SARS-CoV-2 antigens have been detected in most organs. Severe cases of COVID-19 are typically characterized by upregulation of pro-inflammatory cytokines and chemokines, aberrant cellular immune responses, abnormal coagulation indices, respiratory and cardiovascular failure, end organ damage, and even death.[1,3] It is likely that aberrant and excessive immune responses evoked by SARS-CoV-2 infection in the host are involved in the pathogenesis of lung and multi-organ injury.[4,5]

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Conclusion