How Stem Cell Therapy Offers Immune Improvement in COVID-19 Patients
How Stem Cell Therapy Offers Immune Improvement in COVID-19 Patients

In a healthy individual, the immune system is supposed to kick in to fight off viral and bacterial invaders. It comes to our defense, limiting the spread of these threats and helping to reduce symptoms. However, in COVID-19 patients, the immune system seems to struggle to fight off the attacker.

In many cases, the immune system itself becomes part of the problem. While there are as yet no vaccines or effective drugs approved specifically for fighting COVID-19, and supportive treatments remain the norm, stem cell therapy shows great promise in helping the patient’s immune system fight off the infection and even repair damage like scarring of lung tissues.

How Does the Immune System Turn Against the Body?

The most visible example of COVID-19’s ability to turn the human immune system against a patient is the cytokine storm. According to a study published in the journal Nature,

"Notably, while a rapid and well-coordinated immune response represents the first line of defense against viral infection, excessive inflammatory innate response and impaired adaptive host immune defense may lead to tissue damage both at the site of virus entry and at systemic level. Several studies highlight relevant changes occurring both in innate and adaptive immune system in COVID-19 patients. In particular, the massive cytokine and chemokine release, the so-called "cytokine storm", clearly reflects a widespread uncontrolled dysregulation of the host immune defense.

Although the prospective of counteracting cytokine storm is compelling, a major limitation relies on the limited understanding of the immune signaling pathways triggered by SARS-CoV-2 infection. The identification of signaling pathways altered during viral infections may help to unravel the most relevant molecular cascades implicated in biological processes mediating viral infections and to unveil key molecular players that may be targeted."

A second study, this one published in the journal Life Sciences, noted that

"SARS-CoV-2, directly and indirectly, affects the immune system and avoids being eliminated in early stages. On the other hand, the secretion of inflammatory cytokines creates critical conditions that lead to multi-organ failure. The immune system which is affected by the virus tries to respond via a cytokine storm and hyperinflammation, which itself leads to further multi-organ damage and even death."

Stem Cell Therapy: How Might It Help the Immune System?

From the information above, it becomes clear that COVID-19 itself avoids being eliminated while simultaneously triggering the body’s immune system to overreact. The results, a cytokine storm and hyperinflammation, wreak as much damage on the body as the virus itself, perhaps more in some cases. Stem cell therapy shows promise in mitigating cytokine storms and limiting or even eliminating inflammation.

For instance, in a study titled Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV2 pneumonia requiring mechanical ventilation. A proof of concept study, it was found that stem cell therapy resulted in clinical improvement in most patients within mere days of administration.

According to the study’s authors:

"Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 × 106 (IQR 0.50 × 106) AT-MSC/kg of recipient's body weight. Potential adverse effects related to cell infusion and clinical outcome were assessed. Additional parameters analyzed included changes in imaging, analytical and inflammatory parameters.

First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. No adverse events were related to cell therapy. With a median follow-up of 16 days (IQR 9 days) after the first dose, clinical improvement was observed in nine patients (70%). Seven patients were extubated and discharged from ICU while four patients remained intubated (two with an improvement in their ventilatory and radiological parameters and two in stable condition). Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy). Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement.

Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects."

A second study, this one published in Aging and Disease, found similar results. The study’s authors point out,

"Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection.

MSCs could cure or significantly improve the functional outcomes of seven patients without observed adverse effects. The pulmonary function and symptoms of these seven patients were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment.

After treatment, the peripheral lymphocytes were increased, the C-reactive protein decreased, and the overactivated cytokine-secreting immune cells CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, and CXCR3+ NK cells disappeared in 3-6 days. In addition, a group of CD14+CD11c+CD11bmid regulatory DC cell population dramatically increased. Meanwhile, the level of TNF-α was significantly decreased, while IL-10 increased in MSC treatment group compared to the placebo control group.

Furthermore, the gene expression profile showed MSCs were ACE2- and TMPRSS2- which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition."

A Final Note

While stem cell therapy, particularly using allogeneic stem cells sourced from umbilical cord blood, show great promise, patients should understand that these remain experimental. The FDA has not approved any stem cell treatment at this time.

Sources:

MSC Therapies for COVID-19: Importance of Patient Coagulopathy, Thromboprophylaxis, Cell Product Quality and Mode of Delivery for Treatment Safety and Efficacy
Exploring the Utility of Stem Cell Therapy for COVID-19
Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia
Stem cells key in beating COVID-19 says MS Patient
Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study
The immune system and COVID-19: Friend or foe?
Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2

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