COVID-19 caused clusters of severe respiratory illness and was associated with 2% mortality. No specific anti-viral treatment exists. The mainstay of clinical management is largely symptomatic treatment, with organ support in intensive care for seriously ill patients. Cellular therapy, using mesenchymal stem cells has been shown to reduce nonproductive inflammation and affect tissue regeneration and is being evaluated in patients with ARDS. This clinical trial is to inspect the safety and efficiency of mesenchymal stem cells (MSCs) therapy for severe COVID-19.
The Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome corona
virus 2 (SARS-CoV-2) infection has unprecedentedly spread in the worldwide and been declared
as a pandemic by the world health organization. COVID-19 is characterized by sustained
cytokines production and hyper-inflammation, can cause clusters of severe respiratory illness
with a fatality rate around 2-5%. There are currently no prophylactic vaccine and no specific
antiviral treatment agents available recommended for COVID-19. Therefore, it is urgent to
find a safe and effective therapeutic approach to COVID-19.
During the last decade, the promising features of mesenchymal stem cells (MSCs), including
their regenerative properties and ability to differentiate into diverse cell lineages, have
generated great interest among researchers whose work has offered intriguing perspectives on
cell-based therapies for various diseases. These findings seem to highlight that the
beneficial effect of MSC-based treatment could be principally due by the immunomodulation and
regenerative potential of these cells. MSCs could significantly reduce the pathological
changes of lung and inhibit the cell-mediated immune inflammatory response induced by
influenza virus in animal model . MSCs has been shown to reduce nonproductive inflammation
and affect tissue regeneration and is being evaluated in patients with ARDS. Our phase I
preliminary data of parallel assignment study(NCT04252118) showed that three doses of MSCs
was safe in patients with COVID-19. Randomized control trial is needed to assess efficacy and
safety.
The investigators will do a prospective, double-blind, multicentre, randomised trial to
assess treatment with three intravenous doses of MSCs compared with placebo. 90 severe
COVID-19 patients will be recruited in China. 60 patients will receive i.v. transfusion 3
times of MSCs (4.0*10E7 cells per time) and the standard of care as the treated group. In
addition, the 30 patients will receive placebo and standard of care as control group.
Change in lesion proportion (%) of full lung volume from baseline to day 10, day28 and 90,
change in consolidation/ ground-glass lesion proportion (%) of full lung volume from baseline
to day 10, 28 and 90, time to clinical improvement in 28 days, mMRC (Modified Medical
Research Council) dyspnea scale, 6-minute walk test, maximum vital capacity (VCmax),
Diffusing Capacity (DLCO), oxygen saturation, oxygenation index, duration of oxygen therapy,
side effects, immunological characteristics (immune cells, inflammatory factors, etc.) will
be evaluated during the 90 days follow up.
Biological: UC-MSCs
3 does of UC-MSCs(4.0*10E7 cells per time) intravenously at Day 0, Day 3, Day 6.
Biological: Saline containing 1% Human serum albumin（solution without UC-MSCs）
3 does of placebo（intravenously at Day 0, Day 3, Day 6）
Inclusion Criteria:
1. Male or female, aged at 18 years (including) -75 years old
2. Hospitalized
3. Laboratory confirmation of SARS-CoV-2 infection by reverse-transcription polymerase
chain reaction (RT-PCR) from any diagnostic sampling source
4. Pneumonia that is judged by computed tomography
5. In accordance with any one of the following : 1)dyspnea (RR ≥ 30 times / min),
2)finger oxygen saturation ≤ 93% in resting state, 3)arterial oxygen partial pressure
(PaO2) / oxygen absorption concentration (FiO2) ≤ 300MMHG, 4)pulmonary imaging shows
that the focus progress > 50% in 24-48 hours
6. Interstitial lung damage is judged by computed tomography.
Exclusion Criteria:
1. Pregnancy, lactation and those who are not pregnant but do not take effective
contraceptives measures;
2. Patients with malignant tumor, other serious systemic diseases and psychosis;
3. Patients who are participating in other clinical trials;
4. Inability to provide informed consent or to comply with test requirements.
5. Co-Infection of HIV, tuberculosis, influenza virus, adenovirus and other respiratory
infection virus.
6. Invasive ventilation
7. Shock
8. Combined with other organ failure( need organ support)
9. Interstitial lung damage caused by other reasons ( in 2 weeks)
10. The pulmonary imaging revealed the interstitial damage of lungs before the COVID-19
confirmed.
General Hospital of Central Theater Command
Wuhan, Hubei, China
Maternal and Child Hospital of Hubei Province
Wuhan, Hubei, China
Wuhan Huoshenshan Hospital
Wuhan, Hubei, China
Fu-Sheng Wang, MD, PhD, Study Chair
Beijing 302 Hospital