ABSTRACT
In late December 2019, some cases of acute respiratory illness occurred in Wuhan, Hubei province, China that caused by a virus named "severe acute respiratory syndrome 2" (SARS-Cov2). More susceptible patients to this disease are elderly male patients since these patients with comorbid diseases are disposed to severe infection and more death. The most important comorbid diseases with COVID-19 pneumonia are hypertension, diabetes mellitus, cerebrovascular disease, chronic obstructive pulmonary disease, coronary heart disease. The most common symptoms of SARS-Cov2 infection are dyspnea, cough, fatigue, diarrhea and vomiting. High number of kidney disease in hospitalized patients with COVID-19 has been reported. Furthermore, a large group of patients with COVID-19 pneumonia had signs of kidney disease, with a high level of serum creatinine and blood urea nitrogen that could be justified with different pathophysiologies happened in COVID-19 pneumonia. However, massive differences were found in the prevalence of acute kidney injury (AKI) in patients with acute respiratory distress syndrome (ARDS) secondary to COVID-19 pneumonia, since various studies have shown that AKI correlates with higher mortality rate, upper morbidity and more severe cases of illness. Therefore, we should be informed about the pathophysiology of AKI in COVID-19 pneumonia to find the modalities to decrease the incidence of AKI and subsequent decrease mortality and morbidity of this disease.Copyright © 2021 The Author(s).
ABSTRACT
Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are characterized by an inflammatory response, alveolar edema, and hypoxemia. ARDS occurs most often in the settings of pneumonia, sepsis, aspiration of gastric contents, or severe trauma. The prevalence of ARDS is approximately 10% in patients of intensive care. There is no effective remedy with mortality high at 30-40%. Most functional proteins are dynamic and stringently governed by ubiquitin proteasomal degradation. Protein ubiquitination is reversible, the covalently attached monoubiquitin or polyubiquitin moieties within the targeted protein can be removed by a group of enzymes called deubiquitinating enzymes (DUBs). Deubiquitination plays an important role in the pathobiology of ALI/ARDS as it regulates proteins critical in engagement of the alveolo-capillary barrier and in the inflammatory response. In this review, we provide an overview of how DUBs emerge in pathogen-induced pulmonary inflammation and related aspects in ALI/ARDS. Better understanding of deubiquitination-relatedsignaling may lead to novel therapeutic approaches by targeting specific elements of the deubiquitination pathways.
Subject(s)
Acute Lung Injury/metabolism , Deubiquitinating Enzymes/metabolism , Respiratory Distress Syndrome/metabolism , Animals , Humans , Pneumonia/metabolism , Signal Transduction/physiology , Ubiquitin/metabolism , Ubiquitination/physiologyABSTRACT
WHAT IS KNOWN AND OBJECTIVE: This article summarizes the effects of sivelestat on acute lung injury/acute respiratory distress syndrome (ALI/ARDS) or ARDS with coagulopathy, both of which are frequently seen in patients with COVID-19. COMMENT: COVID-19 patients are more susceptible to thromboembolic events, including disseminated intravascular coagulation (DIC). Various studies have emphasized the role of neutrophil elastase (NE) in the development of DIC in patients with ARDS and sepsis. It has been shown that NE inhibition by sivelestat mitigates ALI through amelioration of injuries in alveolar epithelium and vascular endothelium, as well as reversing the neutrophil-mediated increased vascular permeability. WHAT IS NEW AND CONCLUSIONS: Sivelestat, a selective NE inhibitor, has not been evaluated for its possible therapeutic effects against SARS-CoV-2 infection. Based on its promising beneficial effects in underlying complications of COVID-19, sivelestat could be considered as a promising modality for better management of COVID-19-induced ALI/ARDS or coagulopathy.