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1.
ERS Monograph ; 2021(94):86-100, 2021.
Article in English | EMBASE | ID: covidwho-2322531

ABSTRACT

The series of autopsies reported since the beginning of the pandemic have highlighted several patterns of lung damage, both isolated and combined. The factors influencing the occurrence of these different tissue responses to viral aggression by SARS-CoV-2 have not yet been determined. In asymptomatic patients or patients with respiratory symptoms who were not ventilated, lymphocyte pneumonia associated with type II pneumocyte atypical hyperplasia and a few hyaline membranes or focal lesions of acute fibrinous pneumonia have been observed. In critically ill patients, the most frequent pattern is diffuse alveolar damage with interstitial lymphoid infiltration, type II pneumocyte atypia and, very often, capillary or arteriolar microthromboses and/or endothelitis. The precise description of these lesions, which is becoming more and more consensual, makes it possible to understand the favourable effects of corticosteroid therapy in seriously ill patients and the evolution under ventilation towards fibrosis.Copyright © ERS 2021.

2.
Klinicka Mikrobiologie a Infekcni Lekarstvi ; 27(4)(4):135-141, 2021.
Article in Czech | EMBASE | ID: covidwho-2321777

ABSTRACT

Treatment of COVID-19 patients and their extreme numbers represented an unprecedented challenge for the intensive care system in healthcare facilities throughout the Czech Republic, a country particularly affected by the new coronavirus SARS-CoV-2 pandemic. A steep increase in the need for intensive care placed an excess burden on bed and staff capacity. For a severe and critical course of COVID-19, bilateral pneumonia with acute hypoxemic respiratory failure is pathognomonic. In the intensive care setting, COVID-19 therapy is primarily symptomatic, supporting failing respiratory function to gain time needed to restore it and to repair the lungs. The aggressiveness and comprehensiveness of respiratory support depend on the severity of failure, ranging from simple oxygen therapy, to non-invasive support and mechanical ventilation, to extracorporeal support. By contrast, specific COVID-19 therapy is directly targeted against SARS-CoV-2 or modulates the organism's response to the virus. Primary, virus-induced lung injury may be secondarily complicated by coinfection or superinfection, most commonly bacterial, increasing the severity and lethality of the disease. Therefore, anti-infective therapy is crucial for the prognosis and outlook of intensive care COVID-19 patients. Among nosocomial infections com-plicating COVID-19, ventilator-associated pneumonia (developing in mechanically ventilated patients) is particularly important and challenging, and so are issues related to bacterial resistance and rational antibiotic therapy.Copyright © 2021, Trios spol. s.r.o.. All rights reserved.

3.
Canadian Journal of Anesthesia. Conference: Canadian Anesthesiologists' Society Annual Meeting, CAS ; 69(Supplement 2), 2022.
Article in English | EMBASE | ID: covidwho-2321635

ABSTRACT

The proceedings contain 63 papers. The topics discussed include: a retrospective study to optimize post-anesthetic recovery time after ambulatory lower limb orthopedic procedures at a tertiary care hospital in Canada;a virtual airway evaluation as good as the real thing?;airway management during in hospital cardiac arrest by a consultant led airway management team during the COVID-19 pandemic: a prospective and retrospective quality assurance project;prevention of cautery induced airway fire using saline filled endotracheal tube cuffs: a study in a trachea airway fire model;smart phone assisted retrograde illumination versus conventional laryngoscope illumination for orotracheal intubation: a prospective comparative trial;time to single lung isolation in massive pulmonary hemorrhage simulation using a novel bronchial blocker and traditional techniques;cannabinoid type 2 receptor activation ameliorates acute lung injury induced systemic inflammation;bleeding in patients with end-stage liver disease undergoing liver transplantation and fibrinogen level: a cohort study;endovascular Vena Cavae occlusion in right anterior mini-thoracoscopic approach for tricuspid valve in patients with previous cardiac surgery;and mesenchymal stem cell extracellular vesicles as a novel, regenerative nanotherapeutic for myocardial infarction: a preclinical systematic review.

4.
Infectious Diseases: News, Opinions, Training ; 11(4):30-37, 2022.
Article in Russian | EMBASE | ID: covidwho-2321333

ABSTRACT

Aim - to study the clinical and laboratory manifestations of a severe course of COVID-19 in a lethal outcome with an assessment of the pathomorphological picture based on autopsy material. Material and methods. A retrospective analysis of demographic, clinical and laboratory parameters, as well as the results of a pathoanatomical study of 54 patients with severe COVID-19 who died in the intensive care unit, was carried out. Results. Among the patients included in the study, women and men were equally divided. The mean age was 73.1+/-1.86 years (median 73 years). An increase in body temperature above 38 degreeS was observed in 81.5% of cases, weakness - in 70.4%, dry cough - in 46.3%, a feeling of lack of air - in 46.3%, muscle pain - in 40.7%. The volume of lung damage by the type of bilateral polysegmental pneumonia with areas of compaction of the type of "frosted glasses" and consolidation was more than 75.0% and was determined in 68.5% of patients. Concomitant diseases were detected in 94.4% of patients. It was found that all patients had a pronounced systemic inflammatory response, as evidenced by an increase in the level of C-reactive protein and procalcitonin in all patients. A decrease in albumin levels was observed in 88.9% of cases. A hypercoagulable shift with intravascular coagulation was noted. Morphological studies revealed damage to the lungs, liver, kidneys and pancreas with the development of thrombovascular changes. Conclusion. A severe course of COVID-19 with a fatal outcome was observed in older patients with clinical, radiological and laboratory manifestations of a systemic inflammatory response, which was accompanied by damage to various organs and systems.Copyright © Authors, 2022.

5.
Infectious Diseases: News, Opinions, Training ; 11(3):12-20, 2022.
Article in Russian | EMBASE | ID: covidwho-2327224

ABSTRACT

The aim of the study was to assess the frequency of symptoms of post-COVID syndrome by means of a questionnaire among medical university employees. Material and methods. From March 2021 to February 2022, an anonymous online survey was conducted at the A.I. Yevdokimov Moscow State University of Medicine and Dentistry of the Ministry of Healthcare of the Russian Federation. Only 313 fully completed questionnaires were selected for analysis. Results and discussion. A wide range of asthenic, infectious-inflammatory, respiratory, cardiovascular, neuropsychiatric, gastroenterological and dermatological symptoms were noted both during the peak period and during the convalescence of COVID-19. According to the subjective data of respondents, for more than 3 months, various symptoms associated with deterioration of health after recovering from a new coronavirus infection persisted in 25.9% of cases. Within 3-6 months after the illness and more than 6 months, 44.6% and 55.4% of respondents noted the presence of symptoms of post-COVID syndrome, respectively. During the analysis, it was found that with an increase in the volume of lung damage according to CT data, there was a tendency to increase the proportion of respondents with a long-term (more than 6 months) persistent symptoms of post-COVID syndrome from 20% with CT score 0, up to 29% with CT score 1-2 and up to 58% with CT score 3-4. In this regard, apparently, it is necessary to develop additional screening programs as part of the medical examination of COVID-19 patients. Conclusion. SARS-CoV-2 infection causes a wide range of symptoms both during the period of the disease and during the period of convalescence. Attention should be paid to the need for a targeted survey of patients who have undergone COVID-19 to identify the manifestations of post-COVID syndrome and conduct their medical examination with the participation of a multidisciplinary team.Copyright © Eco-Vector, 2022.

6.
Yaoxue Xuebao ; 58(4):928-937, 2023.
Article in Chinese | EMBASE | ID: covidwho-2326972

ABSTRACT

Dayuanyin (DYY) has been shown to reduce lung inflammation in both coronavirus disease 2019 (COVID-19) and lung injury. This experiment was designed to investigate the efficacy and mechanism of action of DYY against hypoxic pulmonary hypertension (HPH) and to evaluate the effect of DYY on the protection of lung function. Animal welfare and experimental procedures are approved and in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Science. Male C57/BL6J mice were randomly divided into 4 groups: control group, model group, DYY group (800 mg.kg-1), and positive control sildenafil group (100 mg.kg-1). The animals were given control solvents or drugs by gavage three days in advance. On day 4, the animals in the model group, DYY group and sildenafil group were kept in a hypoxic chamber containing 10% +/- 0.5% oxygen, and the animals in the control group were kept in a normal environment, and the control solvent or drugs continued to be given continuously for 14 days. The right ventricular systolic pressure, right ventricular hypertrophy index, organ indices and other metrics were measured in the experimental endpoints. Meantime, the expression levels of the inflammatory factors in mice lung tissues were measured. The potential therapeutic targets of DYY on pulmonary hypertension were predicted using network pharmacology, the expression of nuclear factor kappa B (NF- kappaB) signaling pathway-related proteins were measured by Western blot assay. It was found that DYY significantly reduced the right ventricular systolic pressure, attenuated lung injury and decreased the expression of inflammatory factors in mice. It can also inhibit hypoxia-induced activation of NF- kappaB signaling pathway. DYY has a protective effect on lung function, as demonstrated by DYY has good efficacy in HPH, and preventive administration can slow down the disease progression, and its mechanism may be related to inhibit the activation of NF-kappaB and signal transducer and activator of transcription 3 (STAT3) by DYY.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.

7.
Infectious Diseases: News, Opinions, Training ; 11(4):38-46, 2022.
Article in Russian | EMBASE | ID: covidwho-2326915

ABSTRACT

Patients with end-stage kidney disease undergoing hemodialysis have one of the highest COVID-19 mortality rates. The use of innovative methods capable of optimizing their treatment outcomes is important for clinical practice. Aims - to investigate the efficacy and safety of neutralizing monoclonal antibodies in COVID-19 patients treated with hemodialysis. Material and methods. We conducted a retrospective controlled single-center study with 102 COVID-19 patients on maintenance hemodialysis involved (M: 67;65.7%;W: 35;34.3%), aged 57.2+/-15.3 years. PCR-detected SARS-CoV-2 infection was diagnosed in all patients. Neutralizing monoclonal antibodies were administered to 69 patients, who formed the study group (group 1). The control group included 33 patients (group 2). The combination of bamlanevimab and etesevimab was the most frequent therapy used (in 59 patients). Results. In the course of the disease, group 1 patients, compared to those of group 2, had statistically significantly higher blood oxygen saturation values (94.2+/-5.7 vs 89.8+/-10.7);they required less frequent oxygen support (29.0 vs 54.5%) and ICU treatment (18.8 vs 48.5%), respectively. Fatal outcomes occurred in 4 (5.8%) of 69 patients who received neutralizing antibodies and in 6 (18.2%) of 33 patients who did not receive the therapy, p<0.05. Except for one patient, all other patients in both groups developed an unfavorable outcome due to progressive lung damage. However, only 4 of 6 (2/3) patients with progressive lung damage died in group 1, whereas the similar course of the disease proved fatal in all cases in group 2. Conclusion. The use of neutralizing monoclonal antibodies in hemodialysis patients is safe and effective when the drugs are administered early, the pulmonary process progression is insignificant and dominant SARSCoV-2 variants are sensitive to them.Copyright © 2022 Tomsk Polytechnic University, Publishing House. All rights reserved.

8.
Infectious Diseases: News, Opinions, Training ; - (1):26-33, 2023.
Article in Russian | EMBASE | ID: covidwho-2326768

ABSTRACT

Aim. An online survey among social network users was conducted to assess the frequency of COVID-19 cases, the spectrum of medications used for treatment, and the subjective assessment of clinical manifestations of the disease. Material and methods. An anonymous online survey was conducted among users of various social networks using a questionnaire created on the SurveyMonkey survey and research platform. During the first month of December 2021, the survey included 23 questions regarding the clinical and demographic characteristics of respondents, the number of COVID-19 cases, clinical manifestations, and severity, as well as the need for medical help and medication. Results. 752 respondents took part in the online survey, more than 70% of them are under 50 years old. Among the respondents 59.73% had a new coronavirus infection (COVID-19). More than 40% of the participants had COVID-19 in the period from September 2020 to April 2021 (2nd wave in Russia). In 79.2% of people, the presence of a new coronavirus infection was confirmed by one of the diagnostic methods: polymerase chain reaction (PCR test), radiography, the presence of antibodies to Ig G/M, and took into account the presence of contact with infected SARS-CoV-2. 411 participants observed any clinical manifestations of the disease. Most often respondents who had COVID-19 indicated weakness, cough, dyspnea, disappearance or decrease in the acuity of smell and taste. The volume of lung tissue damage in 36.5% of cases was less than 25%. The disappearance of any clinical manifestations of the disease immediately after recovery was noted by 32.0% of respondents. Most of the patients (59.2%) sought medical help at the polyclinic, 38.9% had to self-medicate. 71.9% respondents indicated they had been vaccinated against COVID-19, but without specifying the timing and completeness of the course. Side effects after immunization (fever, weakness, soreness, and redness at the injection site) were subjectively assessed by 41.9% of respondents. Conclusion. Among the surveyed respondents, 62.7% of the disease symptoms were mild. The highest number of cases occurred in the 2nd and 4th waves of COVID-19 morbidity in Russia. Most often respondents indicated symptoms of acute respiratory infection. The complete disappearance of clinical manifestations of the disease immediately after recovery was noted by 32.0 % of respondents, and the persistence of symptoms for up to a year - 7.5. More than 70% of the participants in the online survey reported vaccination against COVID-19, but the questionnaire did not include questions about the timing of vaccinations (before or after COVID-19) and the completeness of the course.Copyright © Eco-Vector, 2023. All rights reserved.

9.
Siberian Medical Review ; 2021(6):60-69, 2021.
Article in Russian | EMBASE | ID: covidwho-2326749

ABSTRACT

Aim of study. To evaluate the influence exerted by additional use of a fixed combination of folic acid with pyridoxine hydrochloride and cyanocobalamin in complex therapy for hospitalised patients with COVID-19-associated lung damage on parameters of inflammation and clinical outcomes. Material and methods. A comparative prospective interventional study included 117 patients with a lung lesion volume caused by the SARS-CoV-2 coronavi-rus corresponding to CT-1 and CT-2. The study group included 78 patients who additionally received a fixed combination of 5mg folic acid, 4mg pyridoxine hydrochloride, and 6mug cyanocobalamin three times a day in combination with standard therapy. The comparison group included 39 patients. Results. By days 14-21 of hospitalisation, the main group showed a decrease in the proportion of patients with CT symptoms of "cobblestone appearance" by 26% (p = 0.005) and an increase in the proportion of patients with transformation of viral lung lesions into areas of consolidation of the pulmonary parenchyma by 23% (p <0.001). The effect of a fixed combination of folic acid with vitamins B6, B12 on the achievement of the level of C-reactive protein <20 mg / l by day 7 depending on the red blood parameters and the number of platelets was established (likelihood ratio test in the logistic regression model: 13.925;P = 0.084) as well as the shortening of the time period required to reach the first negative result of the SARS-CoV-2 RNA test (in the linear regression model, R = 0.437;R2 = 0.191;F = 4.552;p = 0.006). Conclusion. The use of a fixed combination of folic acid with vitamins B6, B12 for patients with COVID-19 is associated with earlier achievement of positive dynamics in CT symptoms of lung damage. The additional use of these micronutrients in combination with restoration of red blood count and platelet count improves the odds ratio of an early decrease in serum C-reactive protein, negative result of the SARS-CoV-2 RNA test.Copyright © 2021, Krasnoyarsk State Medical University. All rights reserved.

10.
Infectious Diseases: News, Opinions, Training ; 11(3):44-51, 2022.
Article in Russian | EMBASE | ID: covidwho-2326548

ABSTRACT

The global pandemic of coronavirus infection (COVID-19) has set complex diagnostic tasks for doctors of polyclinics and hospitals. Considering the simultaneous pandemic spread of two infectious diseases - COVID-19 and HIV infection, the problem of studying the clinical features of combined COVID-19/HIV infection becomes urgent. The aim of the study was to determine the features of the diagnosis and course of COVID-19 against the background of HIV infection in patients undergoing inpatient treatment. Material and methods. The study was conducted on the basis of the temporary Clinical Medical Center COVID-19 of the A.I. Yevdokimov Moscow State University of Medicine and Dentistry of the Ministry of Healthcare of the Russian Federation in Moscow from October 2020 to January 2022. The study included 31 233 patients with COVID-19 complicated by pneumonia. To analyze the features of the course of combined COVID-19/HIV infection, a group of 51 HIV-infected patients was identified. The diagnosis of COVID-19 was determined based on the detection of SARS-CoV-2 RNA by PCR in nasal/oropharyngeal smears and/or according to computed tomography of the lungs (CT). During the study, age, gender, anamnesis, objective examination data were analyzed, taking into account the results of CT scans of the chest organs, data from routine laboratory blood tests, oxygen support regimens, treatment outcomes and duration of detection of SARS-CoV-2 RNA. All patients were treated according to the Temporary Clinical Guidelines for the Diagnosis and Treatment of COVID-19, 14 version dated 12/27/2021. Results. The number of patients with combined HIV infection and SARS-CoV-2 out of the total number of hospitalized COVID-19 patients (n=31 233) was 0.16%. Upon admission, 30 (59%) patients reported having HIV infection and receiving antiretroviral therapy (ART). HIV infection was first diagnosed in 21 patients at 2-3 weeks of inpatient treatment. The average age of patients with SARS-Cov-2/HIV co-infection was 1.5 times less than in patients without HIV (41.1+/-5.3 and 64.4+/-10.1, respectively) (p<=0.05). Concomitant pathology (hypertension, type 2 diabetes mellitus, chronic kidney disease and chronic lung diseases) was less common (51%) in the group of combined infection than in the group without HIV (83%). However, in 41% of patients with coinfection, chronic viral hepatitis B, C was detected, in contrast to 0.3% of cases of COVID-19 patients without HIV. 26 (51%) patients were discharged with improvement, while the average bed-day did not differ from patients without HIV infection (13.4+/-4.5 days and 11.7+/-5.2, respectively) (p>=0.05). 7 (24%) patients at the time of discharge (16.8+/-4.2 days) with clinical and laboratory improvement maintained a positive result of PCR RNA on SARS-Cov-2. In 22 (43%) patients with coinfection, hospitalization was fatal for 3 to 21 days of treatment, with ARDS with respiratory and multiple organ failure, which is 3.6 times higher than in patients without HIV infection. The analysis showed that, regardless of the result of PCR on SARS-CoV-2 RNA, in non-specialized hospitals, HIV testing is indicated for young patients with fever for more than 14 days, with lung damage in the form of bilateral interstitial changes according to CT, a history of chronic hepatitis C, B, with progressive severity of the condition on against the background of COVID-19 therapy. Early consultation of an infectious disease specialist, examination of sputum/lavage by PCR for pathogens of opportunistic infections and the appointment of ART and drugs for the treatment of opportunistic diseases will improve the quality of medical care for patients in a non-core HIV hospital will improve the prognosis of COVID-19.Copyright © Eco-Vector, 2022.

11.
Journal of the Medical Association of Thailand ; 104(4):S123-S127, 2023.
Article in English | EMBASE | ID: covidwho-2325770

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has varied clinical and radiographic manifestations. Severe initial viral infection, cytokine release, opportunistic infection and post-viral inflammation may all contribute to progressive symptoms and severe lung injury. Acute fibrinous and organizing pneumonitis (AFOP), a rare pattern of acute lung injury characterized by intra-alveolar fibrin ball, has so far been reported associated with infections, connective tissue diseases, drugs and toxins, hematologic malignancy, altered immune status and inhalation injury. Case Report: The authors report a case of 26-year-old man with severe COVID-19 pneumonia that clinical and radiographic imaging worsened after episode of cytokine storm. The diagnosis of AFOP was confirmed by transbronchial biopsy, and the patient was successfully treated with high-dose corticosteroids. Conclusion(s): AFOP can be found in severe COVID-19 patients especially when clinical deterioration occurs later in disease course. Clinical suspicion is needed for prompt diagnosis and treatment. High-dose corticosteroid is an effective medication.Copyright © 2023 JOURNAL OF THE MEDICAL ASSOCIATION OF THAILAND.

12.
Infectious Diseases: News, Opinions, Training ; 11(3):28-34, 2022.
Article in Russian | EMBASE | ID: covidwho-2325626

ABSTRACT

The COVID-19 pandemic continues to spread despite all the efforts of the medical community. The aim of the study - to identify the features of a new coronavirus infection (COVID-19) with lung tissue damage in men and women receiving inpatient treatment. Material and methods. The method of continuous sampling selected 225 patients admitted to inpatient treatment. The patients were divided in 2 groups: the 1st group - men (n=85), the 2nd group - women (n=140). Statistical processing was carried out using the IBM SPSS Statistics 22.0 program. Results. In a comprehensive study of the features of lung tissue damage by the new coronavirus infection SARS-CoV-2 in men and women was found that women received inpatient treatment more often, after ineffective outpatient treatment, the general serious condition at admission was more typical for women who had a positive result of a PCR-test for the detection of SARS-CoV-2 (p=0.038). In the presence of general clinical manifestations complaints of loss of sense of smell were more often presented by women (p=0.020). According to laboratory studies in the indicators of general clinical and biochemical blood tests, on average men often have higher levels of creatinine (p<0.001), women more often have elevated levels of ESR (p=0.003), erythrocytes (p<0.001), CRP (p=0.042) and decreased hemoglobin (p=0.029). Conclusion. In the first wave of the Wuhan pandemic of the SARS-CoV-2 virus strain women prevailed among patients admitted to inpatient treatment with lung tissue damage after ineffective outpatient treatment (p=0.038). There was a commonality in age and clinical manifestations, of the complaints in women, only loss of sense of smell was more common (p=0.020). The erythrocytosis detected in women, increased ESR and CRP, lower hemoglobin and creatinine levels are not specific for COVID-19. There were no statistically significant differences in the terms of hospitalization and the fatal outcome of the disease between men and women.Copyright © Eco-Vector, 2022.

13.
Rational Pharmacotherapy in Cardiology ; 19(1):4-10, 2023.
Article in Russian | EMBASE | ID: covidwho-2325594

ABSTRACT

Aim. To assess the association of hypertension with the severe forms and fatal outcomes of Coronavirus disease 2019 (COVID-19). Material and Methods. This retrospective cohort study involved adult patients (>=18 years old), admitted to the University hospital 4 of Sechenov University (Moscow, Russia) between 08 April 2020 and 19 November 2020 with clinically diagnosed or laboratory-confirmed COVID-19. The cohort included 1637 patients. The primary outcome was all-cause in-hospital mortality. The secondary outcomes included intensive care unit admission (ICU) and invasive ventilation. Multiple logistic regression was performed to assess the independent association between risk factors and endpoints. Results. A total of 1637 patients were included in the study. 51.80% (n=848) of the subjects were males. The median age was 59.0 (48.0;70.0) years and 55.90% (n=915) had pre-existing diagnosis of hypertension. Patients with hypertension had significantly more severe lung injury based on chest CT scan findings as well as lower oxygen saturation (SpO2). More of them were admitted to ICU and placed on invasive ventilation. The hypertension group also had higher mortality. Age, hypertension, glucose, C-reactive protein and decreased platelet count were independently associated with mortality, hypertension having the strongest association (OR 1.827, 95% CI 1.174-2.846, p=0.008). Age, hypertension, neutrophil count, platelet count, glucose, and CRP were independently associated with ICU admission, with hypertension having the strongest association (OR 1.595, 95% CI 1.178-2.158, p=0.002). Age, hypertension, glucose, CRP and decreased platelet count were independently associated with invasive ventilation, with hypertension having the strongest association (OR 1.703, 95% CI 1.151-2.519, p=0.008).Based on the multiple logistic regression models, odds of death, ICU admission, and invasive ventilation were higher in the hypertension group as compared to the group without hypertension. Conclusion. Hypertension can be an independent predictor of severe COVID-19 and adverse outcomes, namely death, ICU admission, and invasive ventilation in hospitalized patients.Copyright © 2023 Stolichnaya Izdatelskaya Kompaniya. All rights reserved.

14.
Free Radical Biology and Medicine ; 201(Supplement 1):46, 2023.
Article in English | EMBASE | ID: covidwho-2324939

ABSTRACT

Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (COVID-19) pandemic. It is the final outcome of the acute respiratory distress syndrome (ARDS), characterized by an initial exacerbated inflammatory response and ultimate tissue scarring. Energy balance may be crucial for the recovery of clinical COVID-19. Hence, we asked if two key pathways involved in energy generation, AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling and fatty acid oxidation (FAO) could be beneficial. We tested the drugs Metformin (AMPk activator) and Baicalin (Cpt1A activator) in different experimental models mimicking COVID-19 associated inflammation in lung and kidney. We also studied two different cohorts of COVID19 patients that had been previously treated with Metformin. These drugs ameliorated lung damage in an ARDS animal model, while activation of AMPK/ACC signaling increased mitochondrial function and decreased TGF-beta-induced fibrosis, apoptosis and inflammation markers in lung epithelial cells. Similar results were observed with two new indole derivatives IND6 and IND8 with AMPK activating capacity. Consistently, a reduced stay in the intensive care unit was observed in COVID-19 patients previously exposed to Metformin. Baicalin also reduced kidney fibrosis in two animal models of kidney injury, another key target of COVID-19, while in vitro both drugs improved mitochondrial function and prevented TGF-beta-induced renal epithelial cell dedifferentiation. Our results support that strategies based on energy supply may prove useful in the prevention of COVID-19-induced lung and renal damage.Copyright © 2023

15.
Free Radical Biology and Medicine ; 201(Supplement 1):43, 2023.
Article in English | EMBASE | ID: covidwho-2324269

ABSTRACT

Worldwide, up to 8.8 million excess deaths/year have been attributed to air pollution, mainly due to the exposure to fine particulate matter (PM). Traffic-related noise is an additional contributor to global mortality and morbidity. Both health risk factors substantially contribute to cardiovascular, metabolic and neuropsychiatric sequelae. Studies on the combined exposure are rare and urgently needed because of frequent co-occurrence of both risk factors in urban and industrial settings. To study the synergistic effects of PM and noise, we used an exposure system equipped with aerosol generator and loud-speakers, where C57BL/6 mice were acutely exposed for 3d to either ambient PM (NIST particles) and/or noise (aircraft landing and take-off events). The combination of both stressors caused endothelial dysfunction, increased blood pressure, oxidative stress and inflammation. An additive impairment of endothelial function was observed in isolated aortic rings and even more pronounced in cerebral and retinal arterioles. The increase in oxidative stress and inflammation markers together with RNA sequencing data indicate that noise particularly affects the brain and PM particularly affects the lungs. Noise also increased levels of circulating stress hormones adrenaline and noradrenaline, while PM increased levels of circulating cytokines CD68 and MCP-1. The combination of both stressors has additive adverse effects on the cardiovascular system that are based on PM-induced systemic inflammation and noise-triggered stress hormone signaling. We demonstrate an additive upregulation of ACE-2 in the lung, suggesting that there may be an increased vulnerability to COVID-19 infection. The data warrant further mechanistic studies to characterize the propagation of primary target tissue damage (lung, brain) to remote organs such as aorta and heart by combined noise and PM exposure.Copyright © 2023

16.
Journal of Kerman University of Medical Sciences ; 30(2):92-99, 2023.
Article in English | EMBASE | ID: covidwho-2323820

ABSTRACT

Background: There is still no specific treatment strategy for COVID-19 other than supportive management. The potential biological benefits of ozone therapy include reduced tissue hypoxia, decreased hypercoagulability, modulated immune function by inhibiting inflammatory mediators, improved phagocytic function, and impaired viral replication. This study aimed to evaluate the effect of intravenous ozonated normal saline on patients with severe COVID-19 disease. Method(s): In this study, a single centralized randomized clinical trial was conducted on 80 hospitalized patients with severe COVID-19. The patients were selected by random allocation method and divided into two groups A and B. In group A (control group), patients were given standard drug treatment, and in group B (intervention group), patients received ozonated normal saline in addition to the standard drug treatment. In the intervention group, 400 mL of normal saline was weighed by 40 mug/ kg of body weight and was injected into patients within 15 to 30 minutes (80 to 120 drops per minute). This process was done daily every morning for a week. Primary and secondary outcomes of the disease included changes in the following items: length of hospital stay, inflammatory markers including C-reactive protein (CRP), clinical recovery, arterial blood oxygen status, improvement of blood disorders such as leukopenia and leukocytosis, duration of ventilator attachment, and rapid clearance of lung lesions on CT scans. The need for intensive care unit (ICU) hospitalization, the length of ICU stay, and the mortality rate in patients of the two groups was compared. Result(s): According to the results of the initial outcome variable analysis, the probability of discharge of patients who received the normal ozonated saline intervention was 33% higher than patients who did not receive this intervention;however, this relationship was not statistically significant (HR = 0.67, 95%, CI = 0.42-1.06, P value = 0.089). The chance of ICU hospitalization in patients of the intervention group was three times more than that of the comparison group, but this relationship was not significant (odds ratio = 4.4 95% CI = 1.32-14.50, P value = 0.016). The use of ozonated normal saline was found to increase the risk of death by 1.5 times but this relationship was not statistically significant (odds ratio = 1.5, 95% CI = .24-9.75, P value = 0.646). Ozonated normal saline had a significant effect on changes in respiration rate (in the intervention group the number of breaths was decreased) and the erythrocyte sedimentation rate (in the intervention group the erythrocyte sedimentation rate was increased);however, it had no significant effect on other indicators. Conclusion(s): The present study showed that ozone therapy in hospitalized patients with severe COVID-19 could help improve some primary and secondary outcomes of the disease. Governments and health policymakers should make ozone therapy an available care service so that the need for advanced treatment facilities decreases;consequently, this measure may improve patient safety, prevent lung tissue destruction, and control cytokine storms in patients. Additionally, health decision-makers need to aim for the effective clinical improvement of patients, especially severe ones, and the reduction of their mortality. However, further large-scale multicenter studies with larger sample sizes considering drug side effects and other variables influencing the clinical course of COVID-19 can provide more information on the effectiveness and importance of ozone therapy.Copyright © 2023 The Author(s);Published by Kerman University of Medical Sciences.

17.
Creative Cardiology ; 15(1):32-47, 2021.
Article in Russian | EMBASE | ID: covidwho-2323307

ABSTRACT

Introduction. Currently it is well-recognized that tissue markers allow to classify the process of different infectious diseases and help to identify patients' to subclasses and endotypes for clarifying the prognosis and therapy effectiveness. Objective. To detect different COVID-19 course types according to pathophysiological mechanisms, and evaluate clinical, lab and instrumental features of each clinical course. Material and methods. 108 first COVID-19 patients were admitted at special hospital based on Bakoulev National Medical Research Center for Cardiovascular Surgery. The average age of patients was 57.4 +/- 2.3 years, 54.6% of women, the degree of lung damage was 36.2 +/- 2.3%. All patients were identified with C-reactive protein (CRP) and D-dimer. Results. The patients were divided in 4 groups depending on the degree of main pathophysiological process of system inflammatory response (SIR) and hypercoagulation: with inflammatory (1group) (n = 22), coagulation (2 group) (n = 8), inflammatory-coagulation (3 group) (n = 71) and affectless (4 group) (n = 7) types of disease progression. All the 4 groups of the discharged patients were equal in pulmonic parenchymatous tissue damage degree. The level of lactate dehydrogenase (LDH) was significantly higher in patients of group 3 (334.2 +/- 20.6 U/L) compared with LDH in groups 1, 2 and 4 (respectively 264.2 +/- 21.5, 231 +/- 14.2, 206.3 +/- 32.2 U/L, p < 0.01), which indicates more severe damage to the pulmonary parenchyma. In groups 1 and 3, the level of lymphocytes was lower than in groups 2 and 4. In terms of the D-dimer level, the 3rd and 2nd groups did not differ (1537.4 +/- 126.7 and 1682.5 +/- 394.2, respectively, p > 0.05), but its level was significantly higher in the 3rd group compared with the 1st and 4th (359 +/- 32.9 and 309.3 +/- 50.8, p < 0.01). Over the course of staying in hospital the features of each type of disease progression kept preserved. Conclusions. It is possible to accentuate 4 possible development scenario of the COVID-19: the inflammatory one (with SVR manifestation without hypercoagulation), the hypercoagulation one (without SVR activation), the inflammatory-coagulation (active SVR together with hypercoagulation) and affectless type (without SVR and hypercoagulation). The most prevalent type of COVID-19 disease progression is inflammatory-coagulation scenario which is manifested at 65% of patients.Copyright © Creative Cardiology 2021.

18.
Infectious Diseases: News, Opinions, Training ; 10(1):14-23, 2021.
Article in Russian | EMBASE | ID: covidwho-2323126

ABSTRACT

Objective. Evaluation of clinical observation, the course, the risk factors, and treatment options for SARS-CoV-2 infection in hemodialysis patients with end-stage chronic kidney disease. Material and methods. The retrospective, single-center, uncontrolled study involved 231 patients (132 M/99 W) aged 61.7+/-14.7 years with COVID-19 diagnosed. The SPSS software package was used for statistical analysis. Results. 72 (31.2%) of patients died, 68 (94.4%) of them had ARDS as the main cause of death. Comparative analysis in groups with favorable and unfavorable outcomes of the disease showed that age (68.1+/- 13.2 years vs 58.7+/-14.5 years, p<0.0001) and the comorbidity index (8.8+/-2.2 vs 6.2+/-2.6, p<0.0001) were significantly higher in those who have died compared to survivors. According to CT data, they were more likely to have 3rd or 4th-degree lung damage (72.2 vs 36.5%, p<0.0001), and the minimum oxygen saturation index: 67.6+/-12.8 and 87.8+/-10.9%, respectively (p<0.0001). Somorbidity index and the need for invasive ventilation were independent predictors of the fatal outcome of COVID-19. Early administration of monoclonal antibodies to IL-6 (in the first 3 days after hospitalization) in patients with a low prevalence of the pulmonary process (CT stage 1-2) was associated with a significantly lower frequency of fatal outcome. Conclusions. SARS-CoV-2 infection in HD patients is characterized by a high rate of mortality. Predictors of severe disease in this population are comorbidity index and the need for invasive ventilation.Copyright © Infectious Diseases: News, Opinions, Training.

19.
Elife ; 122023 04 18.
Article in English | MEDLINE | ID: covidwho-2327355

ABSTRACT

Proinflammatory agonists provoke the expression of cell surface adhesion molecules on endothelium in order to facilitate leukocyte infiltration into tissues. Rigorous control over this process is important to prevent unwanted inflammation and organ damage. Protein L-isoaspartyl O-methyltransferase (PIMT) converts isoaspartyl residues to conventional methylated forms in cells undergoing stress-induced protein damage. The purpose of this study was to determine the role of PIMT in vascular homeostasis. PIMT is abundantly expressed in mouse lung endothelium and PIMT deficiency in mice exacerbated pulmonary inflammation and vascular leakage to LPS(lipopolysaccharide). Furthermore, we found that PIMT inhibited LPS-induced toll-like receptor signaling through its interaction with TNF receptor-associated factor 6 (TRAF6) and its ability to methylate asparagine residues in the coiled-coil domain. This interaction was found to inhibit TRAF6 oligomerization and autoubiquitination, which prevented NF-κB transactivation and subsequent expression of endothelial adhesion molecules. Separately, PIMT also suppressed ICAM-1 expression by inhibiting its N-glycosylation, causing effects on protein stability that ultimately translated into reduced EC(endothelial cell)-leukocyte interactions. Our study has identified PIMT as a novel and potent suppressor of endothelial activation. Taken together, these findings suggest that therapeutic targeting of PIMT may be effective in limiting organ injury in inflammatory vascular diseases.


Subject(s)
Lipopolysaccharides , Protein D-Aspartate-L-Isoaspartate Methyltransferase , TNF Receptor-Associated Factor 6 , Animals , Mice , Endothelial Cells/metabolism , Endothelium/metabolism , Lipopolysaccharides/metabolism , Signal Transduction , TNF Receptor-Associated Factor 6/genetics , TNF Receptor-Associated Factor 6/metabolism , Protein D-Aspartate-L-Isoaspartate Methyltransferase/genetics , Protein D-Aspartate-L-Isoaspartate Methyltransferase/metabolism
20.
Front Pharmacol ; 14: 1188202, 2023.
Article in English | MEDLINE | ID: covidwho-2326963

ABSTRACT

The flavonoids baicalin and baicalein were discovered in the root of Scutellaria baicalensis Georgi and are primarily used in traditional Chinese medicine, herbal supplements and healthcare. Recently, accumulated investigations have demonstrated the therapeutic benefits of baicalin in treating various lung diseases due to its antioxidant, anti-inflammatory, immunomodulatory, antiapoptotic, anticancer, and antiviral effects. In this review, the PubMed database and ClinicalTrials website were searched with the search string "baicalin" and "lung" for articles published between September 1970 and March 2023. We summarized the therapeutic role that baicalin plays in a variety of lung diseases, such as chronic obstructive pulmonary disease, asthma, pulmonary fibrosis, pulmonary hypertension, pulmonary infections, acute lung injury/acute respiratory distress syndrome, and lung cancer. We also discussed the underlying mechanisms of baicalin targeting in these lung diseases.

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