[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.

[Modulation of endotoxin-induced respiratory splash of granulocytes and monocytes in patients with Familial Mediterranean Fever by iodine-lithium-alpha-dextrin and sodium thiosulfate].

The effect of an endotoxin--E. coli liposaccharide (LPS) of serotype 026:B6--on the respiratory splash (RS) of neutrophils and monocytes in peripheral blood of patients with Familial Mediterranean Fever (FMF) was studied. It is shown that FMF patients have a periodic increase (during an attack) and a decrease (in the period of remission) in endotoxin-induced RS of neutrophils and monocytes. LPS stimulates chemotoxis-induced RS of neutrophils and monocytes in patients both in the period of remission and during the attack equally effectively. Iodine-lithium-alpha-dextrin and sodium thiosulfate have a marked anti-endotoxic effect which manifests with quick neutralization of endotoxin activity on RS of monocytes and neutrophils in FMF patients both during the attack and remission.

[Spontaneous and inducible respiratory burst of monocytes and neutrophils in periodic autoinflammatory fever].

We investigated spontaneous, chemotaxis-, phagocytosis- and proteinkinase C-dependent respiratory burst of neutrophils and monocytes in the whole blood of patients with familial Mediterranean fever (FMF). We also analysed transient activation of neutrophils and monocytes on the level of a single cell using flow cytofluorimetry. It is shown that compared to healthy donors, the respiratory burst of monocytes and neutrophils in the patients is characterized by an increase in both spontaneous and inducible production of free radicals. In FMF patients probability of transient activation of chemotaxis- and phagocytosis-dependent respiratory burst is higher. This has an important influence rather on production of free radical by activated cells than on their number.

[The effect of colcichine and iodine-lithium-alpha-dextrin on the phagocytosis of granulocytes and monocytes in patients with familial Mediterranean fever].

Disturbances in the regulation of phagocytic activity of neutrophils and monocytes (PANM) in whole peripheral blood of patients with familial Mediterranean Fever (FMF), which had not received treatment with colchicines, were determined by quantitative flow cytofluorimetry. The effect of iodine-lithium-alpha-dextrin (armenicum) and colchicine on the PANM in the blood of FMF patients was studied in vitro. The intensity of phagocytosis in populations of neutrophils and monocytes in FMF patients (n = 6) during the remission period is higher than that during the FMF attack (n = 6) and higher than in healthy donors (n = 9). The PANM in patients during the FMF attack is higher compared to that in healthy donors. Iodine-lithium-alpha-dextrin (armenicum) and colchicine inhibited the phagocytosis of effector cells in FMF patients in a dose-dependent and time-dependent manner. It was shown that the suppressive effect of the drugs increased with decreasing bacteria/effector cells ratio.

[Pharmacological modulation of phagocytosis of granulocytes and monocytes in patients with familial Mediterranean fever].

Disturbances in the regulation of phagocytic activity of neutrophils and monocytes (PANM) in whole peripheral blood of patients with Familial Mediterranean Fever (FMF), which had not receive treatment with colchicines, and the effect of drugs from various pharmacological groups on the PANM in the blood of these patients were studied in vitro by quantitative flow cytofluorimetry. A comparative study of the drug action showed that the most effective PANM inhibitors during FMF are colchicine and iodine-lithium-alpha-dextrin (armenicum), while synthetic glucocorticoids and sodium thiosulfate showed low activity and produced no significant effect. It was established that armenicum is capable of modulating the PANM-inhibition effect of colchicine, neutralizing the effect of TNF, and increasing the effect of glucocorticoids. was observed. Sodium thiosulfate produces inhibition of the activity of armenicum.

[The effect of colchicine on the periodicity of the spontaneous and induced respiratory burst of granulocytes and monocytes during familial Mediterranean fever].

The influence of colchicine on the spontaneous and chemotaxis-, protein kinase C-, and phagocytosis-induced respiratory burst of neutrophils and monocytes in the peripheral blood of patients with familial Mediterranean fever (FMF) has been studied. The transient activation of neutrophils and monocytes on the level of a single cell has been monitored by means of flow cytofluorimetry. It is shown that colchicine blocks the induction of chemotaxis-, phagocytosis-, and proteinkinase C-dependent respiratory burst in vitro, as well as the increased pro-oxidant transient activation of neutrophils and monocytes of FMF patients, both in the period of remission and during the FMF attack. Colchicine stimulates the intensity of the spontaneous respiratory burst of neutrophils and monocytes in patients in the course of remission and during the FMF attack. At the same time, the drug effectively suppresses the periodicity of the multidirectional transient activation of the respiratory burst of effector cells during FMF.

[A respiratory splash of monocytes and neutrophils in familial Mediterranean fever].

AIM: To study spontaneous chemotaxis-, phagocytosis-, and proteinkinase C-mediated respiratory splash (RS) of neutrophils and monocytes in colchicin-untreated patients with familial Mediterranean fever (FMF). MATERIAL AND METHODS: Of 17 FMF patients, 8 ones were examined during the attack, 9 patients--in fever-free period. Spontaneous and induced RS of peripheral blood neutrophils and monocytes was investigated with quantitative flow-cytofluorimetric method. RESULTS: Compared to healthy donors, RS is characterized with activation of both spontaneous and induced production of free radicals. The activity and intensity of the RS in FMF was low in the attack vs in the attack-free period but monocytes population has a stable high activity of the RS. CONCLUSION: Activation of neutrophilic RS in FMF patients is characterized by periodicity the direction of which is opposite to induced monocyte activation in the attack and in attack-free interval.