EDITORIAL
REVIEW
The coronavirus disease 2019 (COVID-19) pandemic has drawn attention to new clinical and fundamental issues in the immunopathology of human diseases. Since in COVID-19 it is the ‘‘hyperimmune’’ response, called cytokine storm syndrome, which forms the basis of the pathogenesis of acute respiratory distress syndrome (ARDS) and multiorgan dysfunction in COVID-19, special attention is drawn to the possibility of “repurposing” (drug repurposing) of some widely used for treatment immune-mediated inflammatory rheumatic diseases (IMIRDs) anti-inflammatory drugs, including glucocorticoids (GC), disease-modified anti-rheumatic drugs (DMARDs), biologic agents and ‘‘targeted’’ DMARDs. In the spectrum of cytokines involved in the pathogenesis of cytokine storm syndrome in IMIRDs and COVID-19, great importance is attached to the pro-inflammatory cytokine, interleukin IL-6. The development and introduction into clinical practice of monoclonal antibodies (mAbs) that inhibit the activity of IL-6 are among the major advances in the treatment of IMIRDs, and in recent years, critical conditions within the framework of the cytokine storm syndrome, including in COVID-19. The review discusses the materials of numerous studies devoted to the problems of the efficacy and safety of mAbs to the IL-6 receptor (tocilizumab) and other mAbs that inhibit the activity of this cytokine in COVID-19. Despite the effectiveness of inhibiting IL-6 in patients with severe COVID-19, many theoretical and clinical problems of immunopathology and pharmacotherapy of this disease require further study.
Hemostatic disorders play an important role in the pathogenesis and clinical manifestations of COVID-19. The purpose of the research was a detailed consideration of the pathogenesis, clinical manifestations, and methods of diagnosing and treatment of coronavirus-induced coagulopathy (CIC). At the onset of COVID-19, hypercoagulability is detected, and consumption coagulopathy and disseminated intravascular coagulation (DIC) syndrome are usually observed at later stages of the disease. In the pathogenesis of hypercoagulation in patients with COVID-19, proinflammatory cytokines, hyperfibrinogenemia, increased blood levels of von Willebrand factor, factor VIII, neutrophilic extracellular traps, platelet activation, production of antiphospholipid antibodies, microvesicles are of importance. Laboratory findings show increased plasma concentrations of D-dimer, fibrinogen, a longer prothrombin time and a decrease in the number of platelets. The cumulative incidence of thrombotic complications ranges from 21 to 31%. Thrombosis risk factors are intensive care unit stay, leukocytosis, and a high plasma D-dimer concentration. Differential diagnosing of CIC should be carried out with disseminated intravascular coagulation, sepsis-induced coagulopathy, antiphospholipid, hemophagocytic syndromes, thrombotic microangiopathy, and heparin-induced thromocytopenia. CIC may be complicated by sepsis, antiphospholipid syndrome, hemophagocytic syndrome, thrombotic microangiopathy, and heparin-induced thrombocytopenia.
The main therapy is low molecular weight heparins treatment. Treatment recommendations are provided.
Novel coronavirus infection is predominantly manifests as lung tissue damage. Imaging methods, particularly, chest X-Ray and computed tomography, are of great importance for detecting pulmonary changes and differentiate them with other diseases (mainly other viral pneumonias). In the early disease stages the disease presents on CT with ground glass opacities, consolidations, crazy paving symptom. With time course, they can gradually decrease, evolve into organizing pneumonia or stay stable and even increase in volume with the spread of consolidation and formation of several signs of organizing pneumonia. Although radiological methods show high sensitivity in the detection of pulmonary changes, their specificity and prognostic ability are not so good today. Novel coronavirus infection can be complicated with pulmonary embolism, development thrombosis in situ in pulmonary small vessels, acute heart failure and subsequent development of cardiogenic pulmonary edema, bacterial superinfection, exacerbation or worsening of chronic lung disease and several iatrogenic issues (pneumothorax, pneumomediastinum, hematomas).
In the early stages of the COVID-19 pandemic, many guidelines for the management of patients with new coronavirus infection did not include recommendations for the use of non-invasive ventilation (NIV) due to the concerns that NIV could be accompanied by high tidal volumes that could cause lung damage. In addition, there was an opinion that NIV increases the risk of spreading bioaerosol containing the SARS-CoV-2 virus. At the same time, NIV was widely used in real clinical practice in the management of severe patients with COVID-19 (in some countries, up to 60% of all respiratory support methods). The accumulated experience demonstrates that when applying NIV, the risk of contamination with viral infections is minimized with adequate use of personal protective equipment. To date, the results of a limited number of studies about effectiveness of NIV in hypoxemic acute respiratory failure (ARF) in patients with COVID-19 are available. In most studies, the need for tracheal intubation and hospital mortality, were on average, 20 – 30%, that suggests a fairly high effectiveness of NIV in ARF in patients with COVID-19.
The article is devoted to a review of data on the prevalence and impact of cardiovascular diseases on the course and outcomes of the new coronavirus infection COVID-19. The review examines the relationship between COVID-19 and the functioning of the renin-angiotensin-aldosterone system, the pathophysiological mechanisms of their mutual influence. The analysis of the latest literature data on the safety of taking angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers is presented. The causes and pathophysiological mechanisms of the development of acute myocardial damage in COVID-19 are discussed. The issue of organizing rehabilitation assistance for patients who have undergone COVID-19 is being considered. The main components and features of the COVID-19 rehabilitation program are presented.
ORIGINAL STUDIES
Since the beginning of the COVID-19 epidemic, the European cystic fibrosis society (ECFS) has decided to launch a special ECFS-COVID-19 program to collect information on the of COVID-19 characteristics in the patients with cystic fibrosis (CF). The results of the program should help timely and efficiently provide the patients with CF with the necessary care. Initially, it was assumed that COVID-19 would be severe in CF patients. The aim. Тo assess the prevalence and characteristics of COVID-19 in patients with cystic fibrosis (CF) in the Russian Federation (RF). Methods. 6 cases (4 children and 2 adults) of COVID-19 in Russian CF patients were analyzed. Results. There are 405,843 infected with SARS-CoV-2 in Russia, the incidence of coronavirus infection in Russia was 1.4 cases per 1 thousand people. According to the Ministry of Health of the RF, as of December 2019, there were 3,931 patients with CF (2,823 children and 1,108 adults). The incidence of COVID-19 was 1.5 per 1000 patients with CF (1.4 : 1,000 for children and 1.8 : 1,000 for adults). The incidence was not higher than in the General population. The diagnosis of COVID-19 was confirmed in 4 boys and 2 women, 3 of the patients were infected with Pseudomonas aeruginosa and 2 – with Achromobacter spp. Mild disease was seen in 5 patients including all the children. Pneumonia was registered in 3 patients. One child with COVID-19 had abdominal syndrome. 2 patients – 1 adult and 1 child – needed in-patient care. Additional antibiotics were given to 4 patients, 2 of them received i/v antibiotics. One adult patient was on the lung transplantation waiting list. This woman had long-term oxygen therapy and BiPAP noninvasive respiratory support before the infection with SARS-CoV-2, FEV1 was 24 %pred. Conclusion. Despite the fact that patients with CF are at risk of severe COVID-19, to date, in the described cases, COVID-19 infection has not led to a significant deterioration of the symptoms of CF. Not a single fatal outcome in Russian patients with CF has been recorded.
Analysis of COVID-19 features in individuals who regularly practice aerobic training. Methods. Asymptomatic persons and patients with COVID-19 older than 30 years, 293 people (180 men and 113 women), 214 of them – inhabitants of the Moscow region (the beginning of the sampling – 2nd decade of April 2020) and 79 – inhabitants of the Belgorod region (the beginning of the sampling – 2nd decade of May 2020), adapted (27 people 1st group) and unadapted (266 – control group) to aerobic training (AT). Computer tomography of the chest, RNA test for SARS-CoV-2 in smears from the nasopharynx-oropharynx, the clinical blood sample and level of antibodies to SARS-CoV-2 were studied. The criterion for adaptation to aerobic loads was considered compliance with the rules of the American Heart Association, 2008. Results. Adapted to AT individuals, in contrast to the control group, characterized with the prevalence of asymptomatic (p = 0.045) and absence of severe forms of COVID-19, limited cataral simptoms of the disease (p < 0.001), rare pneumonia with absence (1) or presence (2) of acute respiratory failure (p1 = 0,028; p2 = 0,034), along with lower prevalence of diseases, potentiating this infection (p = 0.03). Conclusion. Patients adapted to AT have less severe course of COVID-19.
The high informative value of chest computed tomography in the diagnosis of pneumonia caused by SARS-CoV-2 is generally recognized, but there is no enough data on the diagnostic capabilities of this method within 5 first days of the clinical manifestations of the disease. The paper presents the results of chest multispiral (multislice) computed tomography (MSCT) of 56 patients with COVID-19 pneumonia in the early days of the disease. The aim of the study was to analyze the semiotics of pathological changes in the lungs in the first days of the onset of clinical symptoms of COVID-19 and to clarify the methodology for conducting MSCT. Methods. The data of chest MSCT of 56 patients with clinical symptoms of a new coronavirus infection SARS-CoV-2 were analyzed. MSCT was carried out in the first 4 – 5 days of the disease. Results. Five variants for the development of the disease were revealed, including atypical, characterized by the prevalence and CT semiotics of lung damage and apparently due to the different response of the patients to SARS-CoV-2 infection. The leading signs of COVID-19 pneumonia in the early stages of the disease were foci of ground glass opacification (GGO), multifocal lesions of the lungs, edema of the interalveolar pulmonary interstitium, which distinguishes it from pneumonia of another etiology. Conclusion. Comparison of MSCT data and the clinical picture of the disease during the first 5 days suggests with high confidence the pneumonia associated with COVID-19. A prerequisite for conducting MSCT in case of suspicion of this type of pneumonia is the implementation of thin 0.5 – 1.5 mm sections, MSCT performance at suspended full inspiration, post-processing of unenhanced tomogram data in MinIP mode.
Pulmonary rehabilitation in COVID-19 patients with pneumonia is associated with better treatment outcomes. However, existing protocols have never been evaluated in randomized control studies. The aim. To evaluate the effectiveness of newly-developed pulmonary rehabilitation protocol compared to basic Russian COVID-19 guidelines for patients with oxygenation index (OI) between 200 and 400 points without IMV. Methods. Based on literature reviews and own clinical experience, standard rehabilitation protocol was designed and tailored for specific needs of low-OI patients. Two clinical centers participated in the study and included total 73 patients in main group. Control group included 73 retrospective patients based in propensity score; this patients received standard protocol of early pneumonia activation from official COVID-19 guidelines. Ten-days clinical outcomes were assessed based on parameter distribution type. Results. Evidence show significant difference in required time of continuous oxygen support in (5.1 ± 3.3 vs 8.0 ± 4.6 days for main and control group respectively. Main group also had mildly better functional. We’ve observed less mortality in main group, but attribute it not to the program, but for growing experience of health professionals and decreased loads on health system. Malignancy as comorbidity was considered a significant cofactor also. Conclusion. New pulmonary rehabilitation protocol improves clinical outcomes in critical COVID-19 patients by decreasing the demand fox oxygen support.
LECTIONS
This publication is devoted to the ultrasound method of lung examination, which has gained particular relevance during the pandemic of the new coronavirus infection 2019. The lecture discusses the general provisions of lung ultrasound, ultrasonic signs of lung damage, features of ultrasound semiotics in the viral nature of lung lesions, differences from the bacterial nature of lung damage, presents aspects of the use of lung ultrasound during the pandemic of the coronavirus infection 2019. The lecture is based on the experience of domestic and foreign researchers, as well as on the authors’ own experience, which demonstrates the value of this method both in intensive care units and in a therapeutic clinic.
CLINICAL PHARMACOLOGY
PRACTICAL NOTES
Clinical signs of COVID-19 infection are non-specific and diagnosis is typically based on comprehensive evaluation of the patient’s history, clinical status, radiological and laboratory findings. A common finding in COVID-19 patients is increased C-reactive protein (CRP), though in some patients, CRP remains within normal range notwithstanding the presence of other criteria of severe disease. We describe two clinical cases of COVID-19 with severe bilateral pneumonia and late increase in CRP. Similar cases re quite challenging for making the diagnosis and indicating the antiinflammatory therapy.
ISSN 2541-9617 (Online)