INTRODUCTION: COVID-19 SEQUELAE

On December, 2019, a severe atypical pneumonia outbreak appeared in Wuhan, China. The World Health Organization isolated the causative agent and called it SARS-CoV-2, or as it is better known: COVID-19. After spreading to the rest of the world, we now are all familiar with the preventive measures for this disease, and what its main symptoms are: fever, coughing, fatigue and respiratory difficulty. In severe cases, patients can develop an acute respiratory distress syndrome, sepsis, thrombosis, hepatic failure, renal failure, encephalitis and other complications. Other symptoms include: diarrhea, constipation and changes in the senses of taste and smell. To top it all, some of these symptoms can persist even when the patient has already been discharged by the hospital.

The truth is that in many cases there has not been a careful follow-up for patients with mild to severe symptoms. After being discharged, patient don´t know exactly what to do, and some of them continue needing supplementary oxygen for many weeks or months. Recent studies show that most patients will continue with at least one of the following symptoms: dyspnea, fatigue, articular pain, thoracic pain, changes in taste or smell, confusion and memory loss. Also, 17 years ago, another coronavirus epidemic (SARS, 2003), showed that some patients continued with respiratory difficulty for years, and that same thing can happen with this new pandemic if we don´t do something to prevent it.

So, the question is: ¿How can we help those patients that continue feeling ill, tired and with breathing difficulty even after weeks or months of treatment?

Regenerative treatment

Investigators have tried to prove the efficacy of respiratory rehabilitation post-COVID-19, with contradictory results. Some issues have been ignored… specifically, the pathological mechanisms of COVID-19 in the lungs. It causes a lot of fibrosis (scar tissue) and damages cells in such a way that it takes a long time to recover. Thus, a mechanistic approach of exercise and deep breathing techniques won´t help in the recovery of these patients. COVID-19 affects the lungs by the following mechanisms:

  • Inflammation: COVID-19 generates many immune complexes and pro-inflammatory cytokines that affect lung tissue and blood circulation
  • Toxicity: COVID-19 secretes toxins that can get into the bloodstream, and affect coagulation.

These same pathophysiological mechanisms can persist for months. But regenerative medicine is a potential therapy to these same problems. Regenerative medicine specializes in detecting damaged tissues in the human body to reestablish and repair their cellular functions. The following are some of the treatment options that we use to treat COVID-19 sequelae.

  • Mesenchymal Stem Cells (MSCs)
  • Exosomes (vesicles secreted by MSCs)
  • Nanomembrane-based Therapeutic Plasmapheresis

Mesenchymal stem cells

Stem cells have gained much attention in the last decade. Revolutionary advances in genetics and regenerative medicine around the world have given as a result MSCs and exosomes. These cells are a treatment option for multiple pathologies because of their anti-inflammatory effects, immunomodulation and regeneration. For COVID-19 they can be used to achieve a balance in immunological cells and to regenerate affected lung tissue.

Mesenchymal Stem Cells can differentiate into specialized cells in the human body, regenerating tissues such as muscles, cartilages, neurons and even lung tissue. These cells can be obtained from different sources such as placenta, adipose tissue or bone marrow. Afterwards, advanced laboratories expand the cells to obtain a high dose, useful for therapeutic applications. The desired effects are the following:

  • Anti-inflammatory effect: diminish the production of pro-inflammatory substances such as cytokines
  • Immunomodulation: regulate the immunological functions, preventing the damage caused by autoimmune complexes
  • Regeneration: secrete growth factors and/or differentiate into a specialized tissue.

Exosomes

Exosomes are extracellular vesicles secreted by mesenchymal stem cells. These substances can be obtained in special cultures or through centrifugation. For their storage they can be kept frozen for long periods of time without losing any therapeutic function. After a careful extraction process takes place, they can be administered intravenously, in the same way as stem cells are. They show an anti-inflammatory and regenerative effects, that appear faster, but don´t last as long as stem cells´ effects. Exosomes can be used in conjunction with stem cells or as an independent treatment option.

Nanomembrane-based therapeutic plasmapheresis

Plasmapheresis is the procedure by which blood is extracted from the body to be filtered, in such a way that immune complexes and toxins are removed from the body, while the “cleansed” blood returns to the body. The innovative device that we use in IMMUNOTHERAPY allows us to perform simple, fast and safe procedures, with minimal adverse effects. By extracting these complexes and toxins, circulation is improved and the viral load is greatly reduced in active COVID-19 infections. As a result, inflammation decreases, and the patient refers better lung capacity and resistance to exercise.

The filter that we use for this procedure is imported from Russia.  The filter separates blood components through multiple overlapping nanomembranes to dispose of specific macromolecules. These membranes consist of a polymeric film with a thickness of 10-15 μ, made of polyethylene terephthalate or polycarbonate, with pores created by argon particles accelerated through a cyclotron. Blood passes through such membranes and pathological substances are trapped, isolated, and removed from the circulation. Once the procedure is finished, the patient can begin any of the regenerative therapies mentioned above with stem cells or exosomes, for a longer and enhanced effect.

Conclusion

Post COVID-19 patients need a rehabilitation protocol that includes regenerative therapies. Each of the aforementioned options are safe and effective procedures that broaden our horizon of therapeutic tools for the treatment of diseases (not only COVID-19). Many are the patients who have benefited and many more could. We just need to share this information. If you have or had COVID-19, we still can help you.