Mesenchymal Stem Cell Therapy for Severe COVID-19

The coronavirus disease, still prevalent throughout the world in 2021 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has affected roughly 184 million people worldwide. (3)  (SARS-CoV-2) more commonly known as COVID-19 has caused more than 4.7 million people worldwide since the beginning of the pandemic with the numbers still increasing.  Although the virological characteristics and pathogenesis (the process by which a disease or disorder develops) has been clarified, there is currently no specific therapeutic measure.  Severe cases of COVID-19 infection can lead to immune disorder and damage to the body's natural immune response.  

Mesenchymal stem cells (MSCs) can serve as a therapeutic tool to regulate the overactive inflammatory response caused by COVID-19.  Many clinical trials involving the use of mesenchymal stem cell therapy have been conducted since the beginning of the pandemic in 2019.  The findings suggest that MSC treatment can significantly reduce lung damage, and improve patient recovery with safety and healthy immune tolerance.

Mesenchymal stem cell therapy has also proven to be a much safer alternative therapy compared to traditional treatments for treating influenza in animal models.

A recent research article published in "Signal Transduction and Targeted Therapy" conducted by Lei Shi et al. has summarized the recent progress of mesenchymal stem cell therapy for COVID-19 and highlighted both the impacts and challenges of the field.

Importance of stem cell therapy for COVID-19

SARS-CoV-2 infection directly leads to immune disorder in both adaptive and innate immune responses. (1)  This inflammatory profile in COVID-19 patients has been well characterized.  According to Lei Shi et al. "Specifically, the proportions of natural killer (NK) cells, CD4 + T cells, and CD8 + T cells significantly decrease."  This results in an inflammatory immune reaction within the lungs that can be detrimental to organ function.

Immune system modulation and therapeutic principles of MSCs

Mesenchymal stem cells (MSCs) are the most widely utilized type of stem cell in clinical practice because they are widely regarded as safe and have the ability to avoid rejection when administered into the body. 

Mesenchymal stem cells (MSCs) exhibit characteristics that suppress the excessive immune response observed in severe COVID-19.  Mesenchymal stem cells (MSCs) regulate the immune system by promoting an inflammatory response when the immune system is under-activated and reducing inflammation when the immune system is overactivated. MSCs can play a key role in preventing the immune system from attacking itself similar to what one may see in many autoimmune disorders. According to a 2013 study conducted by Bernardo et al. MSCs, when exposed to sufficient levels of pro-inflammatory markers (cytokines) respond by promoting an immune-suppressive response to dampen inflammation and promote tissue homeostasis. (2)

"Thus, MSCs may offer a therapeutic option for patients with severe or critical COVID-19, potentially contributing to recovery from lung damage, suppressing the over-activated inflammatory response, and influencing the progression of pulmonary fibrosis. In both animal models and humans, MSC treatment has been observed to reduce pulmonary lesions and inhibit the inflammatory response induced by influenza virus infection." (1)

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Clinical trials show positive results

The study conducted by Lei Shi et al. reviewed several clinical trials testing the effectiveness MSCs for moderate or severe COVID-19, in addition to three trials for patients with acute respiratory distress syndrome. All of these studies determined that mesenchymal stem cell therapy (MSCT) was safe and well-tolerated.

The mesenchymal stem cells (MSCs) utilized in these studies were delivered intravenously and sourced from the umbilical cord tissue, adipose tissue, or bone marrow-derived mononuclear cells.

Participants in the trial experienced an improved fraction of inspired O2 (FiO2) and partial pressure of oxygen (PO2) levels, alongside an improvement in other clinical parameters and a significant reduction in COVID-related symptoms. Inflammatory cytokine levels were seen to lower in several studies. Additionally, one of the studies monitoring the volume of lung fibrosis lesions observed a notable reduction in size. (1)

The rate of adverse events analyzed throughout the study participants suggests that mesenchymal stem cell therapy is safe and could be beneficial for COVID-19 patients.

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Post-acute COVID-19 syndrome explained. (Long-haul COVID-19)

Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long term complications beyond 4 weeks from the onset of symptoms.

Research suggests that 50 to 80 percent of people who recover from COVID-19 experience at least some lingering after-effects 3 months after infection with the coronavirus. Prolonged symptom duration and disability are common in adults hospitalized with a severe form of COVID-19.

Patient interviews show that while 65 percent of people who had been released from the hospital after being treated for a severe form of COVID-19 had returned to full health, 35 percent still had not fully recovered more than 2 weeks after being hospitalized.

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Symptoms of long COVID

People who have once tested positive for COVID-19 may note the following long-term symptoms.

Common long COVID symptoms include:

• extreme tiredness (fatigue)
• shortness of breath
• chest pain or tightness
• problems with memory and concentration ("brain fog")
• difficulty sleeping (insomnia)
• heart palpitations
• dizziness
• pins and needles
• joint pain
• depression and anxiety
• tinnitus, earaches
• feeling sick, diarrhoea, stomach aches, loss of appetite
• a high temperature, cough, headaches, sore throat, changes to sense of smell or taste
• rashes

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Stem cell therapy for long COVID

Cord tissue-derived MSCs (Mesenchymal Stem Cells), have been shown to improve post-acute COVID-19 symptoms by significantly decreasing inflammatory cytokines, modulating the immune system and improving recovery times.

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Treatment goals

The therapeutic uses of stem cells as a potential therapy for a variety of diseases has been immensely explored, the number of clinical trials conducted with Mesenchymal Stem Cells has increased exponentially over the past few years.
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The stated primary goal of our protocol is the marked reduction in the levels of chronic low-grade inflammation for an extended period of time.
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Stem cells have a unique, intrinsic property that attracts them to inflammation in the body. Studies have shown that stem cells can regenerate damaged or diseased tissues, reduce inflammation and modulate the immune system promoting better health and quality of life.
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In regards to post-acute COVID-19 syndrome, patients can expect fewer long term complications, improved recovery time, a reduction in persistent COVID-19 related symptoms & an overall decrease in inflammation throughout the body.

Further treatment strategies and outlook 

Mesenchymal stem cell therapies (MSCT) currently provide both an exciting and challenging opportunity for COVID-19 patients.  MSCs have been shown to be optimal candidates for reducing inflammation, contributing to organ recovery, preventing long-term pulmonary disability, and reducing mortality.  While it is possible to obtain this treatment internationally, participation within the United States is still limited to small-scale clinical trials and is not yet available to the general public.  

References: 

(1) Shi, L., Wang, L., Xu, R., Zhang, C., Xie, Y., Liu, K., Li, T., Hu, W., Zhen, C., & Wang, F.-S. (2021, September 8). Mesenchymal stem cell therapy for Severe covid-19. Nature News. Retrieved September 27, 2021, from https://www.nature.com/articles/s41392-021-00754-6.

(2) Bernardo, M. E., & Fibbe, W. E. (2013). Mesenchymal Stromal Cells: Sensors and Switchers of Inflammation. Cell Stem Cell, 13(4), 392–402. https://doi.org/10.1016/j.stem.2013.09.006

(3) WHO. Coronavirus disease (COVID-2019) situation reports, https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports (2021).