Resolution of the teleconference "Medical Rehabilitation of Patients with Long COVID"

Over 7 000 health care specialists have registered to participate in the Teleconference “Medical Rehabilitation of Patients with Long COVID” whish was held on September 2, 2021 (Kyiv, Ukraine).

Interdisciplinary format of the Teleconference was assured by involvement of speakers from different special fields, such as: infectious disease specialists, cardiologists, neurologists, anesthesiologists.

Eleven main reports were offered to the participants for review and discussion and they were dealing with the following issues:

• Basic pathophysiological mechanisms and phenotype diversity of Long COVID
• Opportunities of medical rehabilitation of post-COVID syndrome
• Peculiarities of progression of viral infections of the nervous system on the background of post-COVID syndrome
• Long-term consequences of the previous COVID-19 infection and ways for correction of neurological and cognitive disorders
• Post-COVID syndrome in the clinical practice of the cardiologist.

Conclusions and decisions based on discussion of reports:

1. Patients dynamic observations have demonstrated that after previous COVID-19 there are disorders of the cardiovascular, nervous, endocrine systems, kidneys, etc. Some patients have such symptoms for a long time or new symptoms appear in several months. In December 2020 NICE offered classification of COVID conditions: acute COVID-19; long-lasting symptomatic COVID-19 (symptoms continuing from 4 to 12 weeks); post-COVID syndrome (symptoms continuing for more than 12 weeks, they may change over time, disappear and appear again, damaging different systems of the body). Post-COVID syndrome was added to the International Statistical Classification of Diseases (ICD-10) in the wording «Post COVID-19 condition». Long COVID is a term that is often used for description of features and symptoms lasting or developing after acute COVID-19 and includes both current symptomatic COVID-19 (acute and permanent) and post-COVID syndrome.

2. At the same time Harvard scientists offered the term “POST-COVID long-hauler”. It means any person diagnosed with coronavirus resulted in COVID-19 who did not return to his/her state of health and functioning 12 weeks after having suffered the disease.

3. Recently published study covering 3762 participants after previous COVID-19 from 56 countries has determined more than 200 symptoms of Long COVID in 10 systems of the body, and 66 of them were observed within seven months. We may say that Long COVID is hiding behind various phenotypes: post-COVID myocarditis, anemia, neurological complications, chronic fatigue syndrome, labored breathing, metabolic disorders, manifestation of neurodegenerative disease. Diversity of clinical manifestations of Long COVID is united with the single complications development mechanism.

4. Three pathophysiological syndromes launch development of post-COVID complications: endotheliitis, system background inflammation, pneumonitis and a significant clinical syndrome – asthenia. Endotheliitis is one of the leading syndromes during COVID‑19 and of triggering mechanisms of the Long-COVID syndrome. Virus SARS-CoV‑2 can infect endothelial cells directly penetrating through ACE-2 receptors and resulting in endothelium diffuse inflammation. The virus is also capable of infecting epithelial cells of human blood vessels. Direct infection of endotheliocytes by the virus or indirect damaging by immune cells, cytokines and free radicals can cause pronounced endothelial dysfunction further resulting in microcirculation disorders, vasoconstriction, development of ischemia of organs, inflammation and tissue edema, pro-coagulation.

5. During post-COVID period the development of system background “smoldering” inflammation appears as a result of damaging of vascular endothelium by cytokines and free radicals during hyperimmune reaction; the patients after recovery had higher concentration of cytokines in blood serum (interleukins 2, 4, 6, 17) in comparison to the control group, and it proves that inflammatory process continues after recovery. Cytokines increase permeability of blood-brain barrier and as a result SARS-CoV‑2 may infect astrocytes and microglia, activate cascade of neuroinflammation and neurodegeneration.

6. Reduction of cytokines and other mediators, reduction of permeability of blood-brain barrier; endothelial function correction; increasing the efficiency of internal antioxidant systems of the organism are important approaches to treatment of “smoldering” system background inflammation and endotheliitis. Elimination of cell energy deficiency, of “smoldering” system background inflammation, of water-electrolytic and metabolic disorders are strategic directions in treatment of long-COVID asthenic syndrome.

7. Prescription of edaravone during Long COVID let us reduce system background inflammation through depression of pro-inflammatory cytokines, neutralizes free radicals and reduces activation of microglia and astrocytes.Edaravone protects endothelium against damaging and activates eNOS, impedes iNOS and nNOS function, and amplifies the adhesive contacts of the endothelium. Edaravone reduces system background inflammation, directly and indirectly, inhibiting the production of pro-inflammatory cytokines IL-1, IL-6, iNOS, TNF-α andmetalloproteinases.

8. COVID-19 is often accompanied by arterial and intracardiac thrombosis, venous thromboembolism. Heart troponin levels can be elevated on the background of COVID-19 even if there is no acute myocardial infarction, so it is not recommended to determine troponin level in patients with COVID-19 without clinical signs of acute coronary syndrome with non-specific symptoms. After acute phase of COVID-19 2,5% of patients have thrombosis and 3,7% of patients have hemorrhage. Rapid increase in the number of COVID-19 long-haulers steadily increases loading over health care system. Edaravone added to the treatment scheme of such patients helps to reduce system inflammation. Fixed combination of L-carnitine and L-arginine will improve the power supply of myocardium and help to eliminate the effects of endotheliitis, to enhance the latter effect it is recommended to take L-arginine aspartate peroral after the infusion therapy.

9. Xylitol-containing electrolytes solution can be assigned to reduce asthenic syndrome, as far as xylitol metabolizes without insulin and provides energy to cells. Ethylmethylhydroxypyridine succinate, identical to the original in composition and instruction, 700 ml per day, helps to eliminate anxiety in patients with Long COVID syndrome.

10. In Ukraine only 14% of patients with arterial hypertension take antihypertensive medication and control their blood pressure. Ukraine ranks first among European countries in terms of stroke incidence. Therefore, there is a need for efficient organoprotection in patients with arterial hypertension realized in four directions: lifestyle modification, effective blood pressure control, statin therapy with achievement of target values of LDL cholesterol and use of additional opportunities to protect the neurovascular unit. The levorotatory isomer of arginine potentially protects target organs of arterial hypertension, including the brain. L-arginine improves the endothelium function, definitely decreases index of peripheral vascular resistance of intracranial arteries.

11. When the infusion therapy regime has to be chosen for a cardiac patient one should take into account the patient’s condition, existence of heart failure and level of its compensation, and presence of other illnesses. But the infusion rate matters both in cardiology and in other spheres. The intravenous infusion with the rate 10 ml/min. may be conducted around the clock. As for the infusion volume, even 500 ml per day are normal and acceptable volume for cardiac patients without decompensated heart failure. It gives a chance to prescribe syndrome-pathogenic treatment scheme for Long COVID for more effective rehabilitation of cardiac patients who have not returned to their previous state of health after COVID-19.

12. Detoxification therapy and correction of water-electrolyte disorders are the main pathogenic directions of treatment of neuroinfections in the context of post-COVID syndrome. The mechanism of the detoxification action of the hyperosmolar crystalloid solution is the improvement of microcirculation and perfusion of tissues, the movement of liquid from tissues into the vascular bed, the stimulation of diuresis and the withdrawal of toxins. It is recommended that an adequate dose be administered to achieve the full effect, such as 200 ml up to 60 kg body weight and 400 ml above 60 kg body weight.

13. Monitoring of respiratory function, cardiac symptoms, state of nervous system and psychological functions is obligatory after acute symptoms of COVID-19, as well as pathogenic and syndromic approach to medical rehabilitation of patients focused on suppression of system background inflammation, improvement of endothelial function and decrease of asthenia signs. Multi-disciplinary in-patient rehabilitation is recommended for patients with moderate or severe post-COVID symptoms for permanent recovery.

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