[The impact of BMI on the course of the acute SARS-COV-2 infection and the risks that emerge during the first year after the hospital discharge. Subanalysis evidence of the AKTIV and AKTIV 2 registries].

BACKGROUND: There is enough evidence of the negative impact of excess weight on the formation and progression of res piratory pathology. Given the continuing SARS-CoV-2 pandemic, it is relevant to determine the relationship between body mass index (BMI) and the clinical features of the novel coronavirus infection (NCI). AIM: To study the effect of BMI on the course of the acute SARS-COV-2 infection and the post-covid period. MATERIALS AND METHODS: AKTIV and AKTIV 2 are multicenter non-interventional real-world registers. The АКТИВ registry (n=6396) includes non-overlapping outpatient and inpatient arms with 6 visits in each. The АКТИВ 2 registry (n=2968) collected  the  data  of  hospitalized  patients  and  included  3  visits.  All  subjects  were  divided  into  3  groups:  not  overweight  (n=2139), overweight (n=2931) and obese (n=2666). RESULTS: A higher BMI was significantly associated with a more severe course of the infection in the form of acute kidney injury (p=0.018), cytokine storm (p<0.001), serum C-reactive protein over 100 mg/l (p<0.001), and the need for targeted therapy (p<0.001) in the hospitalized patients. Obesity increased the odds of myocarditis by 1,84 times (95% confidence interval [CI]: 1,13-3,00) and the need for anticytokine therapy by 1,7 times (95% CI: 1,30-2,30).The  patients  with  the  1st  and  2nd  degree  obesity,  undergoing  the  inpatient  treatment,  tended  to  have  a  higher  probability  of  a  mortality  rate.  While  in  case  of  morbid  obesity  patients  this  tendency  is  the  most  significant  (odds  ratio  -  1,78; 95% CI: 1,13-2,70). At the same time, the patients whose chronical diseases first appeared after the convalescence period, and those who had certain complaints missing before SARS-CoV-2 infection, more often had BMI of more than 30 kg/m2 (p<0,001).Additionally, the odds of death increased by 2,23 times (95% CI: 1,05-4,72) within 3 months after recovery in obese people over the age of 60 yearsCONCLUSION.  Overweight  and/or  obesity  is  a  significant  risk  factor  for severe  course  of  the  new  coronavirus  infection  and  the associated cardiovascular and kidney damage Overweight people and patients with the 1st and 2nd degree obesity tend to have a high risk of death of SARS-CoV-2 infection in both acute and post-covid periods. On top of that, in case of morbid obesity patients this tendency is statistically significant. Normalization of body weight is a strategic objective of modern medicine and can contribute to prevention of respiratory conditions, severe course and complications of the new coronavirus infection.

Contribution of the COVID-19 pandemic to the prognosis of patients with class III-IV heart failure

Aim. To study the survival of patients with New York Heart Association (NYHA) class IIIV heart failure (HF) after a coronavirus disease 2019 (COVID-19) and compare it with a group of similar patients without COVID-19, both during and before the pandemic. Material and methods. A sample of 810 patients with HF of any class was created, who were treated in the HF center at the City Clinical Hospital N 38 in Nizhny Novgorod for the period from March 2019 to March 2020. Patients with NYHA class HF III-IV (n=263) were selected from this sample. The diagnosis was confirmed by echocardiography and chest radiography. At the time of discharge, the 6-minute walk test was <300 meters, while the level of N-terminal pro-brain natriuretic peptide — >300 pg/ml. The group was analyzed from March 2019 to December 2021 with the definition of all-cause mortality depending on prior COVID-19. Results. During 520-day follow-up, 30,8% of NYHA class III-IV patients died, while 16,0% of patients underwent COVID-19, of which 79,25% of patients died during this period. Mortality among patients without prior COVID-19 was 23,3% (p<0,001). The 30-day mortality among those with COVID-19 was 50,0%, while for the year, this parameter was 71,4% (p<0,001). Among patients without COVID-19 and with class III-IV HF, 4,64% died in the first 30 days, and 20,7% of patients died during the year (p<0,001). The results obtained were compared with the data from the EPOCHA-CHF program from 2002 to 2017. Conclusion. Mortality among patients with class III-IV HF after COVID-19 was 3,5 times higher compared with those with class III-IV HF without prior COVID-19. During the COVID-19 pandemic, the mortality rate among patients with class III-IV HF without COVID-19 increased by 2,09 times compared with the pre-pandemic period.

Comparative analysis of echocardiographic and electrocardiographic data of survivors and deceased patients with COVID-19 (sub-analysis of the international register “Dynamics analysis of comorbidities in SARS-CoV-2 survivors”)

Aim. To carry out comparative analysis of echocardiographic and electrocardiographic (ECG) data of survivors and deceased patients with COVID-19 (sub-analysis of the international register “Dynamics analysis of comorbidities in SARS-CoV-2 survivors”). Material and methods. The study presents the results of a sub-analysis of the international AKTIV registry, which was called AKTIV CARDIO. Data were collected from 9 medical centers in the Russian Federation. AKTIV CARDIO included 973 hospitalized patients, of which 50 patients died during hospitalization. Results. Comparative analysis of echocardiographic parameters revealed that 4 parameters differed in deceased patients compared to survivors: left ventricular ejection fraction (LVEF), right ventricular end diastolic dimension (RV EDD), right atrial (RA) short axis diameter and pulmonary artery systolic pressure (PASP). RA short axis diameter was higher in deceased patients compared with survivors (38,0 [36,0;39,0] versus 35,0 [33,0;38,0] mm, p=0,011). RV EDD was higher in deceased patients than in survivors (3,0 [29,0;33,0] vs 28,0 [27,0;32,0] mm, p=0,019). LVEF was lower in deceased patients compared with survivors (55 [52;55] vs 60 [56;65]%, p<0,001). PASP was higher in deceased patients compared with survivors (25 [21;35] vs 20 [19;25] mm Hg, p=0,006). Correlation analysis found that the largest number of correlations with markers of the infection severity was observed for RA short axis diameter and RV EDD. A comparative analysis of ECG data revealed that in deceased patients, compared with survivors, atrial fibrillation (AF) (21,4% vs 6,06%, p=0,001) and supraventricular premature beats (14,3% vs 3,36%, р=0,004) occurred more often. In addition, deceased patients had longer QTc interval (440 [416;450] vs 400 [380;430] ms, p<0,001). Conclusion. Comparative analysis of echocardiographic data showed that deceased patients have more pronounced right heart remodeling, higher PASP and lower LVEF. Patient survival was related to RV and RA sizes. Right heart enlargement was associated with markers of infection severity. Echocardiographic parameters characterizing the right heart side can probably be independent prognostic factors in the acute COVID-19 period.

[ACTIV SARS-CoV-2 registry (Analysis of Chronic Non-infectious Diseases Dynamics After COVID-19 Infection in Adult Patients). Assessment of impact of combined original comorbid diseases in patients with COVID-19 on the prognosis].

AIM: Study the impact of various combinations of comorbid original diseases in patients infected with COVID-19 later on the disease progression and outcomes of the new coronavirus infection. MATERIALS AND METHODS: The ACTIV registry was created on the Eurasian Association of Therapists initiative. 5,808 patients have been included in the registry: men and women with COVID-19 treated at hospital or at home. CLINICALTRIALS: gov ID NCT04492384. RESULTS: Most patients with COVID-19 have original comorbid diseases (oCDs). Polymorbidity assessed by way of simple counting of oCDs is an independent factor in negative outcomes of COVID-19. Search for most frequent combinations of 2, 3 and 4 oCDs has revealed absolute domination of cardiovascular diseases (all possible variants). The most unfavorable combination of 2 oCDs includes atrial hypertension (AH) and chronic heart failure (CHF). The most unfavorable combination of 3 oCDs includes AH, coronary heart disease (CHD) and CHF; the worst combination of 4 oCDs includes AH, CHD, CHF and diabetes mellitus. Such combinations increased the risk of lethal outcomes 3.963, 4.082 and 4.215 times respectively. CONCLUSION: Polymorbidity determined by way of simple counting of diseases may be estimated as a factor in the lethal outcome risk in the acute phase of COVID-19 in real practice. Most frequent combinations of 2, 3 and 4 diseases in patients with COVID-19 primarily include cardiovascular diseases (AH, CHD and CHF), diabetes mellitus and obesity. Combinations of such diseases increase the COVID-19 lethal outcome risk.

Analysis of influence of background therapy for comorbidities in the period before infection on the risk of the lethal COVID outcome. Data from the international ACTIV SARS-CoV-2 registry («Analysis of chronic non-infectious diseases dynamics after COVID-19 infection in adult patients SARS-CoV-2¼).

Aim      To study the effect of regular drug therapy for cardiovascular and other diseases preceding the COVID-19 infection on severity and outcome of COVID-19 based on data of the ACTIVE (Analysis of dynamics of Comorbidities in paTIents who surVived SARS-CoV-2 infEction) registry.Material and methods  The ACTIVE registry was created at the initiative of the Eurasian Association of Therapists. The registry includes 5 808 male and female patients diagnosed with COVID-19 treated in a hospital or at home with a due protection of patients' privacy (data of nasal and throat smears; antibody titer; typical CT imaging features). The register territory included 7 countries: the Russian Federation, the Republic of Armenia, the Republic of Belarus, the Republic of Kazakhstan, the Kyrgyz Republic, the Republic of Moldova, and the Republic of Uzbekistan. The registry design: a closed, multicenter registry with two nonoverlapping arms (outpatient arm and in-patient arm). The registry scheduled 6 visits, 3 in-person visits during the acute period and 3 virtual visits (telephone calls) at 3, 6, and 12 mos. Patient enrollment started on June 29, 2020 and was completed on October 29, 2020. The registry completion is scheduled for October 29, 2022. The registry ID: ClinicalTrials.gov: NCT04492384. In this fragment of the study of registry data, the work group analyzed the effect of therapy for comorbidities at baseline on severity and outcomes of the novel coronavirus infection. The study population included only the patients who took their medicines on a regular basis while the comparison population consisted of noncompliant patients (irregular drug intake or not taking drugs at all despite indications for the treatment).Results The analysis of the ACTIVE registry database included 5808 patients. The vast majority of patients with COVID-19 had comorbidities with prevalence of cardiovascular diseases. Medicines used for the treatment of COVID-19 comorbidities influenced the course of the infectious disease in different ways. A lower risk of fatal outcome was associated with the statin treatment in patients with ischemic heart disease (IHD); with angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor antagonists and with beta-blockers in patients with IHD, arterial hypertension, chronic heart failure (CHF), and atrial fibrillation; with oral anticoagulants (OAC), primarily direct OAC, clopidogrel/prasugrel/ticagrelor in patients with IHD; with oral antihyperglycemic therapy in patients with type 2 diabetes mellitus (DM); and with long-acting insulins in patients with type 1 DM. A higher risk of fatal outcome was associated with the spironolactone treatment in patients with CHF and with inhaled corticosteroids (iCS) in patients with chronic obstructive pulmonary disease (COPD).Conclusion      In the epoch of COVID-19 pandemic, a lower risk of severe course of the coronavirus infection was observed for patients with chronic noninfectious comorbidities highly compliant with the base treatment of the comorbidity.

International register “dynamics analysis of comorbidities in sars-cov-2 survivors” (Aktiv sars-cov-2): Analysis of predictors of short-term adverse outcomes in covid-19

The international AKTIV register presents a detailed description of out-and inpatients with COVID-19 in the Eurasian region. It was found that hospitalized patients had more comorbidities. In addition, these patients were older and there were more men than among outpatients. Among the traditional risk factors, obesity and hypertension had a significant negative effect on prognosis, which was more significant for patients 60 years of age and older. Among comorbidities, CVDs had the maximum negative effect on prognosis, and this effect was more significant for patients 60 years of age and older. Among other comorbidities, type 2 and 1 diabetes, chronic kidney disease, chronic obstructive pulmonary disease, cancer and anemia had a negative impact on the prognosis. This effect was also more significant (with the exception of type 1 diabetes) for patients 60 years and older. The death risk in patients with COVID-19 depended on the severity and type of multimorbidity. Clusters of diseases typical for deceased patients were identified and their impact on prognosis was determined. The most unfavorable was a cluster of 4 diseases, including hypertension, coronary artery disease, heart failure, and diabetes mellitus. The data obtained should be taken into account when planning measures for prevention (vaccination priority groups), treatment and rehabilitation of COVID-19 survivors.

International register “dynamics analysis of comorbidities in sars-cov-2 survivors” (Aktiv) and the register “analysis of hospitalizations of comorbid patients infected during the second wave of sars-cov-2 outbreak” (aktiv 2)

The organizer of the registers “Dynamics analysis of comorbidities in SARS-CoV-2 survivors” (AKTIV) and “Analysis of hospitalizations of comorbid patients infected during the second wave of SARS-CoV-2 outbreak” (AKTIV 2) is the Eurasian Association of Therapists (EAT). Currently, there are no clinical registries in the Eurasian region designed to collect and analyze information on long-term outcomes of COVID-19 survivors with comorbid conditions. The aim of the register is to assess the impact of a novel coronavirus infection on long-term course of chronic non-communicable diseases 3, 6, 12 months after recovery, as well as to obtain information on the effect of comorbidity on the severity of COVID-19. Analysis of hospitalized patients of a possible second wave is planned for register “AKTIV 2”. To achieve this goal, the register will include men and women over 18 years of age diagnosed with COVID-19 who are treated in a hospital or in outpatient basis. The register includes 25 centers in 5 federal districts of the Russian Federation, centers in the Republic of Armenia, the Republic of Kazakhstan, the Republic of Kyrgyzstan, the Republic of Belarus, the Republic of Moldova, and the Republic of Uzbekistan. The estimated capacity of the register is 5400 patients.

Gender Characteristics of the Novel Coronavirus Infection (COVID-19) in Middle-Aged Adults.

The aim of the study is to assess the gender-related specifics of the COVID-19 course in patients under 55 years of age. Materials and Methods: This pilot single-center continuous retrospective non-randomized study was carried out in the repurposed infectious diseases hospital of the Privolzhsky Research Medical University (Nizhny Novgorod, Russia). The study inclusion criterion was the age of patients (up to 55 years) and confirmed coronavirus infection. In the groups based on gender differences (25 men, average age 44.0±7.8 years and 32 women, average age 41.9±9.1 years), we monitored complications of COVID-19 such as the transfer of patients to the ICU and the volume of lung damage (determined with CT scans). Results: The course of COVID-19 in male patients younger than 55 was aggravated by concomitant diseases (γ=0.36; p=0.043), among which IHD (γ=1.00; p=0.003) and liver disease (γ=0.58; p=0.007) dominated. Frequency analysis confirmed the high prevalence of coronary artery disease in men (p=0.044). Significant differences between the gender-related groups were noted in the volume of lung lesions: at admission (p=0.050), during hospital treatment (p=0.019), and at discharge (p=0.044). Using the logistic regression method, a relationship was found between the transfer of male patients to ICU and the Krebs index [y= -2.033 + 1.154 male gender + 1.539 Krebs index (χ2=5.68; p=0.059)] and comorbidity [y= -2.836 + 1.081 male gender + 2.052 comorbidity (χ2=7.03; p=0.030)]. The influence of the Krebs index and the male gender on the excess volume of lung lesions was shown [y= -1.962 + 0.575 male gender + 1.915 Krebs index (χ2=7.78; p=0.021)]. Conclusion: In individuals under the age of 55 diagnosed with COVID-19, gender is of significant importance: in men, there is a more pronounced lesion of the lung parenchyma and a more significant change in laboratory parameters. Risk factors for a severe course of COVID-19 in men are coronary artery disease and hepatobiliary disorder. Calculating the Krebs index can be used to assess the risk of disease progression.

INTERNATIONAL REGISTER “DYNAMICS ANALYSIS OF COMORBIDITIES IN SARS-COV-2 SURVIVORS” (AKTIV SARS-COV-2): ANALYSIS OF 1,000 PATIENTS

COVID-19 is a severe infection with high mortality. The concept of the disease has been shaped to a greater extent on the basis of large registers from the USA, Spain, Italy, and China. However, there is no information on the disease characteristics in Caucasian patients. Therefore, we created an international register with the estimated capacity of 5,000 patients - Dynamics Analysis of Comorbidities in SARS-CoV-2 Survivors (AKTIV SARS-CoV-2), which brought together professionals from the Russian Federation, Republic of Armenia, Republic of Kazakhstan, and Kyrgyz Republic. The article presents the first analysis of the register involving 1,003 patients. It was shown that the most significant difference of the Caucasian population was the higher effect of multimorbidity on the mortality risk vs other registers. More pronounced effect on mortality of such diseases as diabetes, obesity, hypertension, chronic kidney disease, and age over 60 years was also revealed. COVID-19 - тяжелое инфекционное заболевание с высоким риском летального исхода. Представление о болезни во многом сформировано на основании крупных регистров, выполненных в США, Испании, Италии, КНР. Однако к настоящему времени нет данных по особенностям протекания болезни у пациентов евроазиатского региона. В связи с этим был создан международный регистр, расчетная мощность которого составляет 5000 пациентов, “Анализ динамики Коморбидных заболеваний у пациенТов, перенесшИх инфицироВание SARS-CoV-2” (AКТИВ SARS-CoV-2), работа в котором объединила специалистов Российской Федерации, Республики Армения, Республики Казахстан и Кыргызской Республики. В статье представлен первый анализ регистра, который включил данные 1003 пациентов. Показано, что самым значимым отличием евроазиатской популяции пациентов оказалось гораздо большее влияние полиморбидности на риск летального исхода в сравнении с другими регистрами, а также более выраженное влияние на риск летального исхода в евроазиатской популяции таких заболеваний, как сахарный диабет, ожирение, артериальная гипертензия, хроническая болезнь почек и возраста старше 60 лет.

[International register "Analysis of Chronic Non-infectious Diseases Dynamics After COVID-19 Infection in Adult Patients (ACTIV SARS-CoV-2)"]

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[The agreed experts' position of the Eurasian Association of Therapists on tactics of management of patients with comorbid pathology infected with SARS-Cov-2].

The agreement of experts of the Eurasian Association of Therapists (EAT) discusses pathogenesis and treatment of COVID-19. Modern data on the characteristics of cardiovascular, kidney, respiratory damage in SARS-infected CoV-2 are presented. The tactics of managing patients initially having cardiovascular diseases, diabetes mellitus, chronic obstructive pulmonary disease, bronchial asthma, chronic kidney disease are discussed in detail. The article presents data on drug interaction of drugs.

[Use of Statins, Anticoagulants, Antiaggregants and Antiarrhythmic Drugs in Patients With COVID-19. The Agreed Experts' Position of Russian Society of Cardiology, Eurasian Association of Therapists, National Society on Atherothrombosis, Societies of Experts in Urgent Cardiology, Eurasian Arrhythmology Association].

This article discusses relevant aspects in the treatment of patients with COVID-19. Up-to-date information about principles for administration of statins, antithrombotics, and antiarrhythmics is presented. The authors addressed in detail specific features of reversing heart rhythm disorders in patients with coronavirus infection and the interaction of antiarrhythmic and antiviral drugs. Recommendations are provided for outpatient and inpatient antithrombotic therapy for patients with COVID-19. Issues of antithrombotic and antiviral drug interaction are discussed.

[The Agreed Experts' Position of the Eurasian Association of Therapists on Some new Mechanisms of COVID-19 Pathways: Focus on Hemostasis, Hemotransfusion Issues and Blood gas Exchange].

The article discusses pathogenesis and treatment of COVID-19. The authors presented state-of-the-art insight into hemostatic disorders in patients with COVID-19 and clinical recommendations on prevention of thrombosis and thromboembolism in patients infected with SARS-CoV-2. The article discussed in detail a new hypothesis proposed by Chinese physicians about a new component in the pathogenesis of COVID-19, namely, about the effect of SARS-CoV-2 virus on the hemoglobin beta-chain and the formation of a complex with porphyrin, which results in displacement of the iron ion. Thus, hemoglobin loses the capability for transporting oxygen, which aggravates hypoxia and worsens the prognosis. The article stated rules of hemotransfusion safety in the conditions of COVID-19 pandemic.