In a recent study published in Scientific Reports, researchers discuss the results of a multicentric, randomized, placebo-controlled trial to determine the safety and efficacy of normoxic-allogenic umbilical cord mesenchymal stem cells (MSCs) in treating severe coronavirus disease 2019 (COVID-19) patients.
Study: Effectiveness and safety of normoxic allogenic umbilical cord mesenchymal stem cells administered as adjunctive treatment in patients with severe COVID-19. Image Credit: Anusorn Nakdee / Shutterstock.com
Background
COVID-19 is a multifactorial disease caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the disease causes mild respiratory symptoms in most infected individuals, SARS-CoV-2 can induce severe and fatal infections in high-risk individuals, including the elderly, immunocompromised patients, and people with comorbidities.
Hyper-inflammation and the ‘cytokine storm’ are considered key indicators of severe COVID-19, which is associated with significant morbidity and mortality. Cytokine release syndrome caused by the cytokine storm acts together with chemokine release to induce multiorgan failure in severe COVID-19 patients.
MSC therapy has been shown to improve the clinical course of severe COVID-19, primarily through its anti-apoptotic, anti-inflammatory, and immunomodulatory properties.
In addition to its therapeutic potential, another benefit of MSC therapy is its cost-effectiveness. MSCs can be easily prepared from umbilical cord-derived blood, which is easily available in any hospital with a maternity ward. The collection of MSCs is non-invasive and their preparation does not require highly sophisticated equipment.
In this randomized, placebo-controlled trial, scientists investigate the safety and therapeutic efficacy of normoxic-allogenic umbilical cord MSCs as an adjunctive treatment in severe COVID-19 patients.
Study design
A total of 42 patients with severe COVID-19 from three major hospitals in Java, Indonesia, were recruited in this trial. Study participants were randomly divided to either the intervention or placebo control groups, both of which comprised 21 patients each.
In the intervention group, patients received a dose of 1 × 106 MSCs/kg body weight through the intravenous route at days zero, three, and six. In the placebo group, patients received 0.9% sodium chloride (NaCl) at each respective time point.
The primary aim of the trial was to assess the effect of intervention on the duration of hospital stay. The researchers also assessed radiographical progression, respiratory and oxygenation parameters, inflammatory parameters, as well as the safety profile of this treatment.
Important observations
The analysis of the primary trial outcome did not reveal a significant difference in the duration of hospitalization between the intervention and placebo groups.
Chest X-ray analysis indicated that the administration of MSCs reduced radiographical severity at days 15 and 22 following intervention. However, the difference in radiographical severity between the two groups was not statistically significant.
An improvement in dyspnea, which refers to difficulty breathing, was observed in both the groups at 15 and 22 days after treatment initiation. A six-minute walk test performed by the patients from both groups showed comparable scores post-treatment.
Regarding oxygenation parameters, a significant improvement in oxygenation index was observed in the intervention group as compared to the placebo group. These patients also exhibited improvements in their oxygen saturation 22 days after treatment initiation.
Inflammatory profiles of the patients were assessed by comparing blood levels of procalcitonin, a pro-inflammatory marker, between baseline and day 22 in both groups. To this end, MSC treatment caused a significantly smaller induction in procalcitonin levels as compared to the placebo treatment.
A total of 14 patients, seven from each group, died during the treatment period. In both groups, no severe adverse effects were observed until day 91.
Significance
The current study reports that normoxic-allogenic umbilical cord MSCs are safe for treating severe COVID-19 patients. In terms of its therapeutic potency, MSC therapy has been shown to effectively improve oxygenation profiles and suppress inflammation in severe COVID-19 patients.
Patients treated with MSCs exhibited significantly smaller increases in blood procalcitonin levels than those in the placebo group. Although procalcitonin is a well-established diagnostic marker for bacterial infection, high procalcitonin levels in COVID-19 patients is associated with disease severity and mortality. These findings indicate that MSC therapy may have prevented the progression to severe COVID-19 in these patients.
Although no adverse events were observed during the trial period, the imprudent use of MSCs could promote pro-coagulant adverse events that are characterized by thrombo-embolic ischemia or disseminated intravascular coagulation.
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