Stem Cell Therapy Improves Outcome of Patients with COVID19 Pneumonia

March 20, 2020

From Ahvie Herskowitz, MD and Devin Wilson, ND

As the COVID19 pandemic continues so does the search for safe and effective treatment options considering there is currently no cure, vaccine or approved treatment. One possible treatment that has been identified by many scientific and medical groups is stem cell therapy.

Known for their numerous therapeutic actions including repair and regeneration of cells, anti-inflammation and immune modulation, mesenchymal stem cells (MSCs) are one of the most studied types of adult stem cells. MSCs have been used in studies for many lung conditions including chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, pneumonia, etc.

Stem cells can improve the immune microenvironment in the lungs and reduce the risk of pulmonary failure caused by inflammation. Stem cells have the potential of self-renewal and differentiation, and can develop into corresponding functional cells and alveoli, and then repair the damaged tissue.Zuo Wei, head of the research team at the School of Medicine of the Tongji University and the chief scientist of a national research project in China

In January 2020, Robert Chunhua Zhao, from the Life Sciences at Shanghia University led a small, placebo controlled trial to assess the safety and effectiveness of intravenous MSC therapy in patients with COVID19 pneumonia.

“The inflammation and immune damage caused by COVID-19 made me consider the feasibility of using MSCs as a treatment,” said Zhao.

The trial included a total of 10 patients; 7 received MSC therapy and 3 received placebo. Of the 7 patients who received the therapy 2 had common type pneumonia, 4 had severe type and 1 had critically severe type. All 3 patients who received placebo were severe type pneumonia. Of the patients who received the placebo, one died, one became severe and the third had Acute Respiratory Distress Syndrome (ARDS).

Safety outcomes and efficacy outcomes of the treatment group were assessed for 14 days after therapy. Safety outcomes included infusion or allergic reactions, secondary infection and life-threatening adverse events. Primary efficacy outcomes included level of cytokine variation, level of C-reactive protein and oxygen saturation. Secondary efficacy outcomes included total lymphocyte count, chest CT, respiration rate and symptoms.

Separate from safety and clinical outcomes, this study used RNA sequencing to investigate whether or not MSCs themselves could be infected by COVID-19. Their data confirms that MSCs lack the ACE2 and TMPRSS2 receptors required for the COVID19 to infect cells and therefore are immune to it.

IV MSC therapy appears to be safe in COVID-19 patients

No acute treatment related or allergic reactions were observed two hours after MSC treatment. In addition, no delayed hypersensitivity or secondary infections were noted after treatment.

IV MSC therapy improves outcomes of patients with COVID19 pneumonia

Pulmonary function and symptoms including high fever, weakness, shortness of breath, cough and low oxygen saturation were significantly improved in 2-4 days after MSC therapy. Of the 7 patients who received MSC therapy, two patients with common type and one patient with severe type pneumonia recovered and were discharged in 10 days after treatment.

“Seven COVID19 patients, who had MSCs administered via injection, showed improved outcome with no adverse effects. Symptoms of all patients were significantly alleviated within just two days of the treatment. Three patients, including a severe case, were discharged 10 days after treatment.”

After MSC therapy, it was shown that peripheral lymphocytes were increased, C-reactive protein, a common marker of inflammation, was decreased and over-activated immune cells disappeared in 3-6 days. Furthermore, the pro-inflammatory cytokine TNF-alpha decreased significantly and the anti-inflammatory cytokine, IL-10 significantly increased after MSC therapy.

Serial chest CT scans of the critically severe COVID-19 patient shows significant improvement in lung opacity and pneumonia infiltration after MSC therapy. Before therapy lung opacities and pneumonia infiltration occurred in multiple lobes of both lungs. 2 days after MSC therapy pneumonia was seen through the whole lung and 9 days after therapy pneumonia infiltration was largely gone. 14 days after MSC therapy only little opacity was locally residual.

The scans show chest computerized tomography (CT) images of the critically severe COVID-19 patient. On Jan 23, no pneumonia performance was observed. On Jan 30, ground-glass opacity and pneumonia infiltration occurred in multi-lobes of the double sides. Cell transplantation was performed on Jan 31. On Feb 2, the pneumonia invaded all through the whole lung. On Feb 9, the pneumonia infiltration faded away largely. On Feb 15, only little ground-glass opacity was residual locally.

For the critically severe patient, the percentages of over activated immune cells (T cells and NK cells) were remarkably increased compared to healthy controls suggesting an exaggerated immune response and cytokine storm. However, 6 days after MSC therapy these overactive immune cells nearly disappeared and other immune cell subsets were almost reversed to normal levels.

“Evidently, MSCs secrete anti-inflammatory factors to prevent the cytokine storm, suppressing over-active immune response,” said Zhao.

When the overactive immune system attacks a virus, it produces a large number of inflammatory markers over a short period time which can lead to severe cytokine storm and subsequent tissue damage. It is believed that the main reason for the lung damage in COVID-19 may be due to this virus induced exaggerated immune response and cytokine storm.

The authors believe that the immunomodulation and tissue repair properties of MSCs contributed greatly to the improved outcome of COVID-19 patients.
“MSC therapy can inhibit the over-activation of the immune system and promote endogenous repair by improving the microenvironment.”

Zhao et al concluded that “The intravenous transplantation of MSC was safe and effective for the treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition” and that “the improved outcome of COVID-19 patients may be due to regulating inflammatory response and promoting tissue repair and regeneration.”

Since it was launched, the study has treated 31 COVID-19 patients, all showing improvements.

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About Ahvie Herskowitz, MD

Dr. Herskowitz’s extensive training includes a medical degree from The Albert Einstein College of Medicine, residencies in Anatomic Pathology and Internal Medicine, and Fellowship training in Cardiology at The Johns Hopkins Medical Center. During his 12 years at Johns Hopkins, he became Associate Professor of Medicine and Immunology and Molecular Microbiology and led a research team in the study of molecular and immunological mechanisms of inflammation, autoimmunity, ischemia, heart transplantation rejection and congestive heart failure.

Dr. Herskowitz’s latest academic appointment was as Clinical Professor of Medicine at UC San Francisco. To learn more about Dr. Herskowitz, you can read it bio here.

      

About Devin Wilson, ND

Dr. Devin Wilson is a licensed Naturopathic Doctor in the state of California. He treats an array of acute and chronic diseases using a holistic and integrative approach to health. Dr. Wilson is also a health consultant, researcher and writer focusing on anti-aging and longevity medicine including stem cell therapy and exosome therapy.

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