Aim of this prospective, interventional, single-center, randomized study is to evaluate the efficacy and safety of intermittent hypoxic-hyperoxic training (IHHT) as a rehabilitation method in patients with cardiovascular pathology in the early period after coronavirus infection.

The study will include 60 patients with cardiovascular pathology who underwent confirmed by laboratory tests COVID-19 infection 1-3 months ago with the degree of lung lesion CT3, CT4, who were admitted to the University Clinical Hospital No. 4 of I.M. Sechenov First Moscow State Medical University. The patients will be divided into 2 groups (intervention and control groups).

Intervention group will inhale hypoxic gas mixtures (10-12% O2) followed by exposure to a hyperoxic gas mixture with 30-35% O2 5 times a week for 3 weeks, while control group will undergo a simulated IHHT.

All the patients will undergo identical laboratory and instrumental testing before IHHT, after the last IHHT procedure, in a month after the last IHHT procedure and in 6 months.

Estimated result of the study is to confirm or refute the hypothesis of the study that a three-week course of IHHT in patients with cardiovascular pathology in the early period after coronavirus infection can improve exercise tolerance, as well as the quality of life and psychoemotional status, and affect the dynamics of laboratory and instrumental parameters.

Aim of this prospective, interventional, single-centered, randomized study is to evaluate the efficacy and safety of intermittent hypoxic-hyperoxic training as a rehabilitation method in patients with cardiovascular pathology in the early period after coronavirus infection.

The study will include 60 patients with cardiovascular pathology who underwent confirmed by laboratory tests COVID-19 infection (polymerase chain reaction (PCR) testing, enzyme-linked immunosorbent assay (positive result at least 1 time)) 1-3 months ago with the degree of lung lesion CT3, CT4, who were admitted to the University Clinical Hospital No. 4 of I.M. Sechenov First Moscow State Medical University.

Patients will be randomized via the random number table method into two groups, comparable by gender, age and comorbidity:

Intermittent hypoxic-hyperoxic training (intervention group) group, 30 patients who will receive 15 IHHT sessions, 40-minutes long each (5 workouts per week) for 3 weeks. Patients in the IHHT group will inhale hypoxic gas mixtures (10-12% O2) followed by exposure to a hyperoxic gas mixture with 30-35% O2.

A control group of 30 patients will undergo a simulated IHHT course with the same "exposure" time and number of sessions. Patients of this group will breathe normoxic gas mixture using the same equipment; ordinary humidified air is supplied through the mask during the entire session.

Patients eligible for inclusion will undergo the following investigations:

• Anamnesis and complaints collection; physical examination;
• Assessment of the quality of life and psycho-emotional status using the Short Form-36 (SF36) and Hospital Anxiety and Depression Scale (HADS) questionnaires, as well as the six-minute walk test;
• General and biochemical blood tests , urine analysis, , determination of markers of inflammation (ferritin, C-reactive protein, D-dimer, fibrinogen, interleukin-1, interleukin-6, interleukin-18 and tumor necrosis factor), the level of Endothelin-1 and nitric oxide (NO) in the blood;
• Electrocardiography, a flow mediated dilatation procedure for endothelial function assessment,transthoracic echocardiography to identify the structural and functional features of the myocardium, spiroergometry to determine the patient's oxygen consumption.

The statistical processing will be performed using the Python Software Foundation version 3.8 for Windows (Delaware, USA).

Estimated result of the study is to confirm or refute the hypothesis of the study that a three-week course of IHHT in patients with cardiovascular pathology in the early stages after suffering a coronavirus infection can improve exercise tolerance, as well as the quality of life and psychoemotional status, and affect the dynamics of laboratory and instrumental parameters.

Inclusion Criteria:

1. Written informed consent to participate in the study;

2. Age 40 and over;

3. Male and female;

4. One or more cardiovascular pathologies in the anamnesis:

   • a reliably confirmed diagnosis of hypertension, stage I-III (the diagnosis was made in accordance with the National Clinical Guidelines - 2019);
   • stable angina pectoris I-III functional class, confirmed by complaints, anamnesis and physical examination and with the help of diagnostic tests (bicycle ergometry or daily electrocardiography monitoring);
   • confirmed diagnosis of arrhythmias and conduction disorders based on electrocardiography data and 24-hour Holter monitoring (premature depolarization, supraventricular tachycardia, atrial fibrillation, sick sinus syndrome, atrioventricular block I-II, bundle branch blocks);
   • chronic heart failure stage I-IIB, I-III functional class (New York Heart Association Functional Classification), confirmed by the presence of clinical signs and at least one of two criteria: myocardial dysfunction of left ventricle or / and an increase in the level of the N-terminal fragment of brain natriuretic peptide over 125 pg / ml;
   • the presence of signs of systolic or diastolic dysfunction of the left ventricle according to echocardiography.

5. COVID-19 infection confirmed by laboratory tests (polymerase chain reaction testing, enzyme-linked immunosorbent assay (positive result at least 1 time) with a CT degree of 3 or higher.

Non-inclusion criteria:

1. Acute infectious diseases, tuberculosis;
2. Chronic somatic diseases in the acute stage;
3. Congenital anomalies of the heart and large vessels;
4. Valvular heart defects (congenital and acquired);
5. Severe atherosclerosis of the lower extremities'vessels (chronic ischemia of the lower extremities,stage 3-4);
6. Acute decompensated heart failure (II-IV class according to Killip classification);
7. Chronic heart failure IV functional class (New York Heart Association Functional Classification classification);
8. Secondary arterial hypertension;
9. Acute coronary syndrome within 4 weeks before the start of the study;
10. Life-threatening rhythm and conduction disturbances;
11. Bronchial asthma with the development of respiratory failure II-III degree;
12. Acute cerebrovascular accident within the last 4 months;
13. Chronic kidney disease (glomerular filtration rate<30 ml / min / 1.73 m2 via CKD-EPI (chronic kidney disease epidemiology collaboration) formula);
14. Pregnancy;
15. Mental illness (severe dementia, schizophrenia, severe depression, manic-depressive psychosis);
16. Oncology, diagnosed within a year or receiving a course of radiation / chemotherapy for cancer at the present time;
17. Severe cognitive impairment (MOS) and clinically significant anxiety and / or depression (HADS) interfering with observation;
18. Individual intolerance to oxygen deficiency.

Exclusion Criteria:

1. Refusal to further participation in the study;
2. Acute psychotic reactions arising in the process of the study;
3. Exacerbation of chronic diseases, requiring a change in patient management tactics and preventing his or her further participation in the study.

No, as it is prohibited by Local Ethics Committee of I.M. Sechenov First Moscow State Medical University. Any necessary information may be provided after official request to Study Principal Investigator

participant and the specialists who will carry out investigations (blood and urine analysis, electrocardiography, a flow mediated dilatation procedure, transthoracic echocardiography).