A coronavirus pandemic has serious implications for the health of the human population, and these consequences have not yet been fully assessed.
An acute viral disease, such as the coronavirus, can worsen the health of patients with chronic conditions or trigger various pathologies, primarily pulmonary and cardiovascular.
Currently, there are no other measures to prevent the disease, except for self-isolation, and there are no specific medications for its treatment, though many are under investigation. In these circumstances, doctors have to concentrate on overcoming the possible consequences of viral exposure on the patient’s body after the acute stage of the disease has been successfully resolved.
Patients with the following illnesses may require rehabilitation after severe pneumonia or SARS (severe acute respiratory syndrome):
- Lung diseases
- Cardiovascular diseases
- Type 2 diabetes
- Metabolic syndrome
- Hypertension (elevated blood pressure)
- Plus, in elderly patients
One of the methods of rehabilitation after the coronavirus is treatment with mesenchymal stem cells (MSCs), which were effectively used to treat severe COVID-19 associated pneumonia. Therapy based on cell products, together with additional therapies, can give significant results during recovery.
The COVID-19 virus is known to use the angiotensin-converting enzyme 2 (ACE2) receptor to enter cells. Therefore, the lungs, heart, brain, kidneys, intestines, and testicles, which are all known to express ACE2 receptors, are potential targets for the novel coronavirus.
Initially, the virus infects the cells of the respiratory system, where it causes inflammation and cell death. Subsequently, the virus spreads and damages other vital organs and tissues, creating a complex range of pathophysiological changes and symptoms, including respiratory distress, cardiovascular complications, renal failure, etc.
Although the possibility is relatively low, there is also the chance of direct kidney damage (which is associated with cytokine overproduction) in a new coronavirus disease.
Pulmonary Consequences of COVID-19
According to recent data, the SARS-CoV-2 virus can penetrate red blood cells and attack hemoglobin, which deprives the red blood cells of the ability to transport oxygen. That is, it leads to disruption in the transport of oxygen through the bloodstream, followed by the development of symptoms of acute respiratory distress (ARDS) and multi-organ oxygen deficiency. The accumulation of products of this attack, in the lung tissue, is associated with the so-called ground-glass-like lung images. This symptom is observed on computer tomography (CT) scans even in asymptomatic patients with coronavirus.
It is assumed that the main complication, after COVID-19, is specifically to the lungs. The combination of an inflammatory process in the lung (pneumonia) and the use of artificial ventilation can trigger the development of pulmonary fibrosis.
Fibrosis is a pathological growth of connective tissue, due to an immune response to local inflammation. When healthy lung tissue is replaced by connective tissue (scarring), the functioning of the lung deteriorates, and symptoms such as shortness of breath, coughing, weakness, and low exercise tolerance may develop. This condition can develop as a long-term consequence of a viral infection, months after recovery, and years before it is diagnosed.
There is evidence that the virus causes damage to the cardiovascular system. According to the American College of Cardiology, the presence of coronavirus in a patient’s body can precipitate cardiac complications. In particular, 16% of hospitalized patients developed an arrhythmia, while other reports indicate cases of acute-onset heart failure, heart attack, and cardiac arrest after the viral infection.
A statistical report on a group of patients hospitalized with COVID-19 found that more than 7% developed an acute cardiac injury. In contrast, patients in the intensive care unit (ICU) had a higher risk (>20%) of having cardiac injury compared to non-ICU patients.
There was evidence of myocardial injury, and 12.5% of COVID-19 patients had cardiac abnormalities similar to myocarditis.
Also, there are warnings about heart-related damage due to the use of medications such as hydroxychloroquine alone or in combination with azithromycin.
Neurological Disorders Caused by COVID-19
Coronaviruses, as a group of related viruses, have already been suspected of harming the central nervous system.
As for the new virus, COVID-19, its entry into the bloodstream allows it to penetrate the cerebral circulation. An additional pathway for the virus to enter and affect the brain is via the cribriform plate close to the olfactory bulb. Patients affected by the virus have reported neurological symptoms such as headache, dizziness, myalgia, anosmia, ataxia, seizures, and other more severe signs of a lesion.
There is evidence of the development of encephalopathy due to viral brain damage. Scientists suppose that the long-term effects of the neuroinvasive nature of the virus may lead to an increased risk of neurodegenerative diseases. Also, patients with COVID-19 that have pre-existing neurological disorders such as Parkinson’s disease or multiple sclerosis are likely to experience a worsening of their condition.
Thromboembolic Complications in COVID-19 Patients
According to significant data and studies, viral damage from COVID-19 is accompanied not only by an inflammatory reaction but also by microvascular thrombosis in predisposed individuals. The medical histories of many patients infected with coronavirus showed they had disseminated intravascular coagulation (DIC). DIC is a condition where clots form due to increased blood coagulation, blocking vessels. The so-called endothelial thrombo-inflammatory syndrome can affect the microvascular bed of the brain, as well as other vital organs.
Blockage of the pulmonary vessels may be associated with respiratory and/or heart failure. Also, the large number of reports of strokes in COVID-19-positive individuals can be explained by the high thromboembolic risk of a new coronavirus.
In the process of patient recovery, specific measures may be required to restore their affected health. First, a damage assessment and a complete check-up of the patient’s overall health status is performed. Diagnostics include (according to indication):
- Blood tests (lipidogram parameters, glucose levels, inflammatory process indicators, immune status, condition of organs, etc.)
- High-resolution computed tomography (HRCT)
- Ultrasound and electrocardiogram
- Plus, other diagnostic measures
Based on the results and depending on the patient’s medical needs, an individual rehabilitation program is developed with a focus on the lungs, heart, kidney failure, and/or neurological disorders.
The inclusion of specific procedures in the rehabilitation program depends on the diagnosis, the severity of the injuries, the general health condition of the patient, and the prognosis. In most cases, we use at least the following therapies, as they have already proven effective in recovery from severe viral pneumonia and its consequences:
- Intravenous administration of activated cell product-MCSs (for systemic regenerative and anti-inflammatory effect).
- Intracellular metabolism recovery (IMR) therapy.
- Interval hypoxic-hyperoxic therapy (IHHT).
- Plasmapheresis and other therapeutic procedures.
We are going to describe these therapies in the text below.
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Post-viral complications are associated with an excessive immune response (due to a cytokine storm), as well as viral damage to tissues. Related to this, mesenchymal stem cells (MSCs) are an excellent therapeutic choice due to their regenerative and immunomodulatory properties. They protect the lungs from acute respiratory distress syndrome (ARDS) by secreting antibacterial peptides and anti-inflammatory cytokines.
After intravenous transplantation of MSCs, a significant population of cells accumulates in the lungs, which can protect alveolar epithelial cells, reclaim the pulmonary microenvironment, prevent pulmonary fibrosis, and cure lung dysfunction. This result is in addition to their immunomodulatory effect.
In general, introduced stem cells enhance the survival and renewal of healthy local cells and help to restore lost functions in tissues and organs.
Additional Therapies for Rehabilitation
1. Intracellular metabolism recovery (IMR) therapy is an individually selected combination of useful substances (trace elements, amino acids, vitamins, and others) administered intravenously. Once in the patient’s bloodstream, this therapeutic compound:
- Delicately cleanses the body of toxins, pathological proteins, pathogenic bacteria, and other factors that cause mitochondrial dysfunction.
- Enhances the transport of vitamins and microelements, which reach the cells and take part in cell metabolism.
- Neutralizes the destructive effects of free radicals, by penetrating through the cell membrane.
- Increases reparative functions and expands the impact of cell therapy two to three times and prolongs its effect.
2. Interval hypoxic-hyperoxic therapy (IHHT) destroys worn-out, old mitochondria and accelerates the formation of healthier, physiologically younger mitochondria in the cells. This effect is due to the strengthening of ventilation in the alveoli, simplification of sputum evacuation, activation of the body’s antioxidant system, improvement of blood flow in tissues and organs. Also, hypoxic therapy:
- Improves cardiorespiratory fitness;
- Improves cognitive function;
- Promotes weight loss, which is accompanied by a reduction of total cholesterol, LDL, and GPN, optimization of blood pressure, and increased hypoxic stability.
3. Plasmapheresis (plasma exchange, Stanford protocol). This procedure allows the quick removal of biological products from the bloodstream and tissues, for example, the breakdown of bacteria, viruses, and virus-damaged cells, and the result of the immune response to the viral exposure. Plasmapheresis also improves respiration and cell nutrition, increases organ blood flow, and activates the regeneration processes, which helps to restore the normal functioning of the body after disease and enhances the patient’s well-being.
4. Other additional therapies may be prescribed, as specified, and include xenon gas, oxygen therapy, intravenous laser/ultraviolet blood therapy, etc.
List of References
Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia. Zikuan Leng, Rongjia Zhu, Wei Hou, Yingmei Feng, Yanlei Yang et al. Aging and disease. 2020, Vol. 11. Issue (2) : 216-228.
Pathophysiological Characteristics and Therapeutic Approaches for Pulmonary Injury and Cardiovascular Complications of Coronavirus Disease 2019. Yong-Jian Geng, Zhi-Yao Wei, Hai-Yan Qian, Ji Huang, Robert Lodato, and Richard J. Castriotta. Cardiovasc Pathol. 2020 Apr 17 : 107228.
Kidney involvement in COVID-19 and rationale for extracorporeal therapies. Claudio Ronco & Thiago Reis. Nature Reviews Nephrology (09 April 2020).
COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism. Wenzhong Liu, Hualan Li. A preliminary report.
Advances in the research of mechanism of pulmonary fibrosis induced by Corona Virus Disease 2019 and the corresponding therapeutic measures. Wang J, Wang BJ, Yang JC, Wang MY, Chen C, Luo GX, He WF. Zhonghua Shao Shang Za Zhi. 2020 Mar 16;36(0):E006.
COVID-19 Clinical Guidance For the Cardiovascular Care Team. The American College of Cardiology. March 6, 2020.
Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. Shaobo Shi, Mu Qin, Bo Shen, et al. JAMA Cardiol. Published online March 25, 2020.
Ventricular Arrhythmia Risk Due to Hydroxychloroquine-Azithromycin Treatment For COVID-19. Timothy F. Simpson, Richard J. Kovacs, and Eric C. Stecker. Cardiology Magazine. Mar 29, 2020.
Possible Central Nervous System Infection by SARS Coronavirus. Kwok-Kwong Lau, Wai-Cho Yu, Chung-Ming Chu, Suet-Ting Lau, Bun Sheng, and Kwok-Yung Yuen. Emerg Infect Dis. 2004 Feb; 10(2): 342–344.
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Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis. Ciceri F, Beretta L, Scandroglio AM, Colombo S, Landoni G et al. Crit Care Resusc. 2020 Apr 15.
Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. Tang N, Li D, Wang X, Sun Z. J Thromb Haemost. 2020 Apr;18(4):844-847.
Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young. Thomas J. Oxley, J. Mocco, Shahram Majidi, Christopher P. Kellner, Hazem Shoirah et al. April 28, 2020. DOI: 10.1056/NEJMc2009787.
Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ et al. Thromb Res. 2020 Apr 10.
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Intermittent Hypoxia-Hyperoxia Conditioning Improves Cardiorespiratory Fitness in Older Comorbid Cardiac Outpatients Without Hematological Changes: A Randomized Controlled Trial. Dudnik E, Zagaynaya E, Glazachev OS, Susta D. High Alt Med Biol. 2018 Dec;19(4):339-343.
Intermittent Hypoxia-Hyperoxia Training Improves Cognitive Function and Decreases Circulating Biomarkers of Alzheimer’s Disease in Patients with Mild Cognitive Impairment: A Pilot Study. Serebrovska ZO, Serebrovska TV, Kholin VA, Tumanovska LV, Shysh AM et al. Int J Mol Sci. 2019 Oct 30;20(21).
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Medical Advisor, Swiss Medica doctor