Hypokalemia and the renin-angiotensinaldosterone system activity in COVID-19 patients

Background. Hypokalemia is a common electrolyte complication among hospitalized patients with pneumonia caused by a new coronavirus SARS-CoV-2. Hyperactivation of the renin-angiotensin-aldosterone system (RAAS) is suggested as a possible cause of hypokalemia in patients with COVID-19.Objective. To investigate the RAAS activity in COVID-19 patients with and without hypokalemia and its possible association with treatment outcomes.Design and methods. The cross-sectional cohort study included 172 patients with COVID-19 pneumonia. Potassium, aldosterone and venous renin were measured in 77 patients. The differences in the levels of acute phase proteins, the degree of lung damage and the severity of COVID-19 were compared between patients with and without hypokalemia.Results. Hypokalemia was found in 19 of 77 patients (25%): the median potassium level in hypokalemia and eukalemia group was 3,1 [2,8–3,3] and 4,1 [3,9–4,5] mmol/L, respectively (p = 0,001). Plasma aldosterone and renin levels in patients with and without hypokalemia did not differ significantly: aldosterone 76,0 [57,7–121,5] and 70,9 [26,3–113,8] pg/ml (p = 0,23), renin 17,0 [8,5–47,2] and 11,0 [6,5–38,1] pg/ml (p = 0,35), respectively. Differences in the degree of lung tissue damage, acute phase proteins, severity of COVID-19, length of hospitalization and mortality in patients with and without identified electrolyte disturbances were also not significant.Conclusions. Our results showed that there were no laboratory signs of RAAS hyperactivation in COVID-19 patients with registered hypokalemia. Identification of the cause and clinical significance of hypokalemia among patients with COVID-19 needs to be specified.

Human Antibody Domains and Fragments Targeting Neutrophil Elastase as Candidate Therapeutics for Cancer and Inflammation-Related Diseases

Neutrophil elastase (NE) is a serine protease released during neutrophil maturation. High levels of NE are related to lung tissue damage and poor prognosis in cancer; thus, NE is a potential target for therapeutic immunotherapy for multiple lung diseases and cancers. Here, we isolate and characterize two high-affinity, specific, and noncompetitive anti-NE antibodies Fab 1C10 and VH 1D1.43 from two large phage-displayed human Fab and VH libraries. After fusion with human IgG1 Fc, both of them (VH-Fc 1D1.43 and IgG1 1C10) inhibit NE enzymatic activity with VH-Fc 1D1.43 showing comparable inhibitory effects to that of the small molecule NE inhibitor SPCK and IgG1 1C10 exhibiting even higher (2.6-fold) activity than SPCK. Their epitopes, as mapped by peptide arrays combined with structural modeling, indicate different mechanisms for blocking NE activity. Both VH-Fc and IgG1 antibodies block NE uptake by cancer cells and fibroblast differentiation. VH-Fc 1D1.43 and IgG1 1C10 are promising for the antibody-based immunotherapy of cancer and inflammatory diseases.

Respiratory muscle strength in patients after COVID-19

Respiratory muscles (RM) are a very important part of the respiratory system that enables pulmonary ventilation. This study aimed to assess the post-COVID-19 strength of RM by estimating maximum static inspiratory (MIP or PImax) and expiratory (MEP or PEmax) pressures and to identify the relationship between MIP and MEP and the parameters of lung function. We analyzed the data of 36 patients (72% male; median age 47 years) who underwent spirometry, and body plethysmography, diffusion test for carbon monoxide (DLCO) and measurement of MIP and MEF. The median time between the examinations and onset of COVID-19 was 142 days. The patients were divided into two subgroups. In subgroup 1, as registered with computed tomography, the median of the maximum lung tissue damage volume in the acute period was 27%, in subgroup 2 it reached 76%. The most common functional impairment was decreased DLCO, detected in 20 (55%) patients. Decreased MIP and MEP were observed in 5 and 11 patients, respectively. The subgroups did not differ significantly in MIP and MEP values, but decreased MIP was registered in the second subgroup more often (18%). There were identified no significant dependencies between MIP/MEP and the parameters of ventilation and pulmonary gas exchange. Thus, in patients after COVID-19, MIP and MEP were reduced in 14 and 31% of cases, respectively. It is reasonable to add RM tests to the COVID-19 patient examination plan in order to check them for dysfunction and carry out medical rehabilitation.

ПЕРЕБІГ ГОСТРОЇ РЕСПІРАТОРНОЇ ХВОРОБИ COVID-19 УСКЛАДНЕНОЇ НЕГОСПІТАЛЬНОЮ ПНЕВМОНІЄЮ НА ТЛІ ПАТОЛОГІЇ СЕРЦЕВО-СУДИННОЮ СИСТЕМИ

The outbreak of the COVID-19 infection caused by the new coronavirus SARS-CoV-2 is one of the most significant and dangerous challenges of our time. To date, there is a decrease in the number of cases per day, but there is a variety in the course of the disease depending on sex, and the most vulnerable are elderly patients with comorbid pathology, therefore, the study of its features determines the relevance of this work. The aim of the research was to study the course of acute respiratory disease COVID-19, complicated by pneumonia, its gender features and the presence of a comorbid cardiovascular pathology. We examined 104 patients with acute respiratory COVID-19 disease, complicated by community-acquired pneumonia. We conducted general clinical methods of research, determined the SARS-CoV-2 virus RNA by PCR and chest X-ray in 2 projections or computed tomography (CT) to identify the features of the lung tissue damage. Among the cardiovascular pathology (35%) we observed coronary heart disease: stable angina pectoris FC (functional class) II-III - 85%, postinfarction cardiosclerosis - 30%, hypertension - 65%. Thus, a more pronounced intoxication syndrome of the variety of symptoms among women with acute respiratory COVID-19 disease, complicated by community-acquired pneumonia, is observed in women than in men, which must be taken into account, both in the diagnosis and treatment, assessment of prognosis of the development of the disease. The presence of a comorbid pathology of the cardiovascular system complicated the course of the underlying disease. It had a more pronounced clinical course in a combination of two or more diseases and was characterized by progressive arrhythmias, subendocardial myocardial ischemia, volume overload of the left and right ventricles. A combination of several comorbid conditions was the most unfavorable for a patient, since it increased the risk of community-acquired pneumonia, was accompanied by its severe course with the development of complications and lethal outcome.

LL-37 and HMGB1 induce alveolar damage and reduce lung tissue regeneration via RAGE

The receptor for advanced glycation end-products (RAGE) has been implicated in the pathophysiology of chronic obstructive pulmonary disease (COPD). However, it is still unknown whether RAGE directly contributes to alveolar epithelial damage and abnormal repair responses. We hypothesize that RAGE activation not only induces lung tissue damage but also hampers alveolar epithelial repair responses. The effects of the RAGE ligands LL-37 and HMGB1 were examined on airway inflammation and alveolar tissue damage in wild-type and RAGE deficient mice and on lung damage and repair responses using murine precision cut lung slices (PCLS) and organoids. Additionally, their effects were studied on the repair response of human alveolar epithelial A549 cells, using siRNA knockdown of RAGE and treatment with the RAGE inhibitor FPS-ZM1. We observed that intranasal installation of LL-37 and HMGB1, induces RAGE-dependent inflammation and severe alveolar tissue damage in mice within 6 hours, with stronger effects in a mouse strain susceptible for emphysema compared to a non-susceptible strain. In PCLS, RAGE inhibition reduced the recovery from elastase-induced alveolar tissue damage. In organoids, RAGE ligands reduced the organoid-forming efficiency and epithelial differentiation into pneumocyte-organoids. Finally, in A549 cells, we confirmed the role of RAGE in impaired repair responses upon exposure to LL-37. Together, our data indicate that activation of RAGE by its ligands LL-37 and HMGB1 induces acute lung tissue damage and that this impedes alveolar epithelial repair, illustrating the therapeutic potential of RAGE inhibitors for lung tissue repair in emphysema.

Comparative characteristics of histological changes in lung tissue in rats of different ages under conditions of hyperhomocysteinemia

Annotation. Defeat of the respiratory system is a common phenomenon in today's conditions. Elevated levels of homocysteine (Hz) are one of the predictors of bronchopulmonary pathology. In recent years, there has been an association between its concentration in blood plasma and the risk of developing COPD, bronchial asthma, lung cancer. The pathogenesis of respiratory damage in hyperhomocysteinemia (GHz) is still being studied, but it is known to be the cause of endothelial dysfunction, oxidative stress, endoplasmic reticulum stress, which underlie lung tissue damage. The aim of the study is to establish a comparative characterization of histological changes in the lung tissue of rats of different ages at GHz. The experimental study was performed on 64 white nonlinear male rats. During the experiment, the animals were divided into two groups – control and experimental, each of which is divided into subgroups depending on age – young (1-2 months), mature (6-8 months), old (24-26 months). Simulation of the stable GHz state was achieved by administering to rats the experimental group thiolactone Hz at a dose of 200 mg/kg body weight intragastrically for 60 days. Histological specimens were studied using an SEO CCAN light microscope and photo-documented using a Vision CCD Camera with an image output system from histological specimens. Histological examinations of the lungs of young animals under GHz conditions revealed moderate destructive changes of vessels, bronchi, components of the respiratory department, which were compensatory-adaptive and reversible. Adaptive-compensatory and destructive changes of the organ were found in adult rats at experimental GHz. Older animals develop the most significant destructive-degenerative changes compared with studies of the lungs of groups of young and mature rats. The defining feature for this age group was excessive activation of fibroblasts and the development of perivascular, peribronchial, interstitial sclerosis.

Practical aspects of using exercise therapy methods for the rehabilitation of patients with COVID-19

In the article it is discussed about the approved methods of using physical therapy on patients with different forms of COVID-19 at the stage of inpatient treatment. The study involved 86 patients with varying degrees of lung tissue damage (CT2CT4), the main group included 49 patients, and the control group included 37 patients. A scheme of rehabilitation measures that can be used in patients with SARS-CoV-19 is proposed. Methods of therapeutic and respiratory gymnastics for both passive and active work with patients to restore muscle strength, improve sputum outflow, prevent deep vein thrombosis and bedsores with various degrees of lung tissue damage are described. The importance of performing physical therapy techniques in the early stages, when the patient is still in bed, is shown. Using the modified Questionnaire "quality of life" (GAD-9), the effectiveness of respiratory and therapeutic exercises was confirmed.

Fungal Lung: The Risk of Fungal Exposure to Nail Care Professionals

Foot and nail care specialists spend a great portion of their day using nail drills to reduce nail thickness and smooth foot callouses. This process generates a large amount of dust, some of which is small enough to breathe in and deposit into the deepest regions of the respiratory tract, potentially causing health problems. Foot and nail dust often contain fungi, from both fungally-infected and healthy-looking nails. While the majority of healthy individuals can tolerate inhaled fungi, the immune systems of older, immunocompromised, and allergy-prone individuals often react using the inflammatory TH2 pathway, leading to mucus overproduction, bronchoconstriction, and, in severe cases, lung tissue damage. To protect vulnerable podiatry professionals, wearing a surgical mask, using a water spray suppression system on nail drills, installing air filtration systems, and considering drilling technique can help reduce the exposure to nail dust.

Use of monoclonal antibodies to IL-6 in patients with severe COVID-19

The use of monoclonal antibodies against interleukin-6 (IL-6) receptors is considered as a potential method of treatment and prevention of complications of the new coronavirus infection 2019 (COVID-19), based on reducing the intensity of the cytokine storm. The aim. To assess the relationship between the use of IL-6 blockers and the risk of tracheal intubation in patients with severe pneumonia associated with COVID-19. Methods. The retrospective cohort study included patients over 18 years of age admitted to the intensive care unit (ICU) with confirmed COVID-19 infection, lung tissue damage of at least 25% between November 4, 2020 and December 25, 2020. All patients underwent standard therapy in accordance with the current recommendations of the Ministry of Health of the Russian Federation, including IL-6 blockers in some patients. The primary endpoint was tracheal intubation and initiation of mechanical ventilation (MV). Data on the use of IL-6 inhibitors, baseline demographic, clinical and laboratory characteristics, as well as information on tracheal intubation, fatal outcomes and length of hospitalization were obtained from the unified medical information and analytical system of the city of Moscow. To analyze the relationship between the use of IL-6 blockers and endpoints adjusted for baseline characteristics, a multivariate Cox proportional hazards model was used. Results. The study included 242 patients, in 120 (49.5%) of them IL-6 blockers were used. The independent predictors of tracheal intubation were the degree of lung tissue damage, ferritin and diabetes, while the use of IL-6 blockers was not associated with a decrease in the risk of intubation: hazard ratio (HR) 0.96 (95% confidence interval [CI] 0.63 – 1.48) and death: HR 1.05 (95% CI 0.69 – 1.62). Subgroup analysis showed that, among surviving patients, the use of IL-6 blockers was associated with an average decrease in hospital stay by 3 days (95% CI 1 – 6 days). Conclusion. The use of IL-6 blockers was not associated with a decrease in the risk of tracheal intubation or death. Among surviving patients, the use of IL-6 blockers was associated with a decrease in the length of hospital stay. These findings may contribute to medical decision making during COVID-19 pandemic associated high hospital workload.

The Many Faces of Innate Immunity in SARS-CoV-2 Infection

The innate immune system is important for initial antiviral response. SARS-CoV-2 can result in overactivity or suppression of the innate immune system. A dysregulated immune response is associated with poor outcomes; with patients having significant Neutrophil-to-Lymphocyte ratios (NLR) due to neutrophilia alongside lymphopenia. Elevated interleukin (IL)-6 and IL-8 leads to overactivity and is a prominent feature of severe COVID-19 patients. IL-6 can result in lymphopenia; where COVID-19 patients typically have significantly altered lymphocyte subsets. IL-8 attracts neutrophils; which may play a significant role in lung tissue damage with the formation of neutrophil extracellular traps leading to cytokine storm or acute respiratory distress syndrome. Several factors like pre-existing co-morbidities, genetic risks, viral pathogenicity, and therapeutic efficacy act as important modifiers of SARS-CoV-2 risks for disease through an interplay with innate host inflammatory responses. In this review, we discuss the role of the innate immune system at play with other important modifiers in SARS-CoV-2 infection.