: The ongoing COVID-19 pandemic has spurred relentless research efforts aimed at unraveling the intricate mechanisms underlying the viral infection. In this pursuit, one area of increasing interest is the role of organokines, a diverse group of signaling molecules produced by various organs and tissues in the human body. These organokines, including adipokines, osteokines, myokines, hepatokines, and cardiokines, have been identified as key players in the complex interplay between organ systems and the viral infection. They exhibit a multifaceted impact on immune responses, inflammation, metabolism, and other physiological processes. Understanding the role of organokines in COVID-19 has significant implications for disease severity, prognosis, and potential therapeutic strategies.
Main steps involved in the pathophysiology of COVID-19 and the possible roles of the organokines in these processes. Inflammation, immune dysregulation, and oxidative stress are part of the infection caused by SARS-CoV-2. Together, they can drive acute respiratory distress syndrome (ARDS) and multi-organ disorders. Organokines can play a role in the occurrence of these phenomena. Understanding how organokines may be involved in developing COVID-19 will certainly contribute to developing new and modern diagnostic and therapeutic strategies for healthcare people infected by SARS-CoV-2. ↑, increase; ↓, decrease; TNF-α, factor tumor necrosis alfa; IL-1β, interleukin 1 beta; IL-2, interleukin 2; IL-6, interleukin 6; IL-8, interleukin 8; IL-10, interleukin 10; CRP, c reactive protein; VEGF, vascular endothelial growth factor; IFN-γ, interferon gamma; and ROS, reactive oxygen species
This COVID-19 News
report covers an extensive study review by researchers from University of Marília (UNIMAR)-Brazil on the role of various organokines in COVID-19.
Organokines in COVID-19 Pathophysiology
To comprehend the significance of organokines in COVID-19, it is crucial to first grasp the pathophysiology of the disease. The SARS-CoV-2 virus, responsible for COVID-19, enters host cells by binding to angiotensin-converting enzyme 2 (ACE2) receptors, primarily found in nasal and bronchial epithelial cells and type 2 pneumocytes in the lungs. This binding initiates a cascade of immune responses, leading to a hyperinflammatory state known as a cytokine storm. The dysregulation of the immune system, characterized by an overproduction of pro-inflammatory cytokines, can result in acute respiratory distress syndrome (ARDS) and multiple organ failure.
Organokines, produced by various organs and tissues, play a vital role in modulating inflammation, immune responses, and disease progression. Changes in the secretion pattern of these molecules can either mitigate or exacerbate the viral infection and predict disease severity. Specific organokines are associated with endothelial dysfunction, multiple organ failure, and increased SARS-CoV-2 viremia. Moreover, organokines are linked to adipocyte dysfunction, which can further contribute to the severity of COVID-19. These findings emphasize the potential of organokines as biomarkers for predicting the severity of COVID-19 and its outcomes.
The Impact of Comorbidities on COVID-19
Patients with pre-existing comorbidities such as diabetes, obesity, hypertension, cardiovascular diseases, liver injury, malignancy, renal diseases, asthma, and chronic pulmonary obstructive disease (COPD) are at higher risk of developing severe COVID-19 symptoms and experiencing complications. The dysregulation of organokines in these individuals, combined with the impact of the virus on their respective organ systems, amplifies the severity of the disease. It is essential to recognize that organokines are key players in the complex relationship between comorbidities and COVID-19.
Innovative Diagnostic and Therapeutic Strategies
The researchers have concluded that a deeper understanding of organokines and their role in COVID-19 may pave the way for innovative diagnostic and therapeutic strategies. Monitoring the levels of specific organokines may enable healthcare professionals to predict disease progression and tailor treatment plans accordingly. Interventions targeting the modulation of organokines could offer new avenues for managing the inflammatory response and mitigating the harmful effects of COVID-19. The potential of organokines in improving patient outcomes and providing personalized approaches to combat the virus is an exciting prospect.
The Role of Adipokines in COVID-19
, a subgroup of organokines primarily produced by adipose tissue, are central to understanding the complexities of COVID-19. These adipokines, which include apelin, omentin, adiponectin, and leptin, have garnered significant attention for their multifaceted roles in the viral infection.
, the most abundant secreted adipokine in humans, plays a pivotal role in various metabolic and non-metabolic processes. It regulates fatty acid oxidation, glucose uptake, vasodilation, inflammation, and fibrosis. Adiponectin levels in COVID-19 patients have been found to vary based on disease severity, with lower levels associated with respiratory failure and severe hyperglycemic events. However, higher levels of adiponectin are observed in severely affected individuals. The adiponectin/leptin ratio has shown promise in discriminating COVID-19-related pneumonia. Remarkably, SARS-CoV-2 can replicate in adipocytes, causing inflammation and altering adipokine secretion, including adiponectin. This dysregulation may contribute to the paradoxical relationship between adiponectin levels and insulin resistance observed in obese individuals with COVID-19.
, another significant adipokine, exhibits endocrinological roles in various organs and systems. It promotes vasodilation, reduces blood pressure, enhances glucose uptake, and contributes to anti-thrombotic effects. The utilization of the ACE2 receptor by SARS-CoV-2 during cell entry has sparked interest in apelin as a potential therapeutic target. By suppressing the production of angiotensin II (Ang-II) and downregulating ACE2 upregulation, apelin and its analogs may counteract the acute lung and cardiovascular injuries caused by elevated Ang-II levels during COVID-19.
, primarily produced by adipocytes, acts as both a hormone and a cytokine. It plays a vital role in regulating energy balance and has immunological implications. Leptin levels in COVID-19 patients have been associated with disease severity, decreased lymphocyte count, and disease progression. High levels of leptin predict severe disease outcomes, but leptin resistance in obese individuals may impair the early immune response against SARS-CoV-2. The dysregulation of leptin and pro-inflammatory cytokines contributes to a hyperinflammatory state, which may explain the increased severity observed in obese individuals with COVID-19.
, an adipokine with anti-inflammatory properties, has been linked to obesity and various metabolic disorders. In COVID-19 patients, elevated levels of progranulin have been observed and correlated with disease prognosis. This adipokine shows promise as a biomarker for COVID-19 and is associated with circulating vascular cell adhesion molecules, further highlighting its involvement in the disease.
The Potential of Adipokines in COVID-19 Management
The role of adipokines in COVID-19 highlights their potential as biomarkers for disease severity and prognosis. Monitoring adipokine levels in COVID-19 patients may aid in identifying individuals at higher risk for severe complications and guide treatment decisions. Additionally, targeting specific adipokines, such as apelin, in therapeutic interventions may offer innovative strategies for managing inflammation and mitigating the harmful effects of COVID-19.
Myokines: The Hidden Heroes in COVID-19
, a class of organokines produced by skeletal muscles, have recently emerged as powerful secretory molecules with the potential to influence various organ systems and physiological processes. These myokines are not only essential for muscle function and movement but also possess regulatory effects on metabolic health, cognitive function, and bone health. In the context of COVID-19, understanding the role of myokines has become increasingly important.
Irisin, one of the key myokines, is induced by exercise and has been associated with promoting energy expenditure and the browning of white adipose tissue. It not only affects muscles but also plays a role in neuroplasticity and bone health. Reduced levels of irisin have been observed in COVID-19 patients, potentially due to the virus's impact on skeletal muscle. This reduction may contribute to fatigue, muscle weakness, and the overall debilitation observed in severe cases of the disease.
Myostatin, a negative regulator of muscle mass, has been shown to be elevated in COVID-19 patients. This elevation is associated with muscle wasting and overall loss of muscle mass, a common complication in severely ill patients. Myostatin inhibitors, under investigation for the treatment of muscle-related diseases, could potentially have a role in mitigating muscle wasting and weakness in COVID-19 patients.
IL-15, an anti-inflammatory myokine, has garnered interest due to its potential to suppress pro-inflammatory cytokines, modulate the immune response, and promote immune cell function. IL-15 therapy has been suggested as a possible treatment approach to mitigate the hyperinflammatory state observed in COVID-19. Through its interaction with the IL-15 receptor, it may prevent or alleviate the cytokine storm and associated lung injury.
Myokines have a profound impact on various physiological processes that are altered during COVID-19 infection. Understanding their roles and the consequences of their dysregulation could provide valuable insights into the disease's pathophysiology and potential therapeutic strategies.
The Impact of Osteokines in COVID-19
are another category of organokines that play a crucial role in bone health and overall physiology. These signaling molecules are produced by osteoblasts, osteocytes, and osteoclasts, contributing to bone remodeling, mineral homeostasis, and the regulation of systemic metabolic processes. Notably, the effects of osteokines extend beyond bone physiology and can influence various aspects of health, including metabolic regulation and immune function.
Osteocalcin, one of the well-known osteokines, is involved in bone mineralization and calcium homeostasis. Beyond its role in skeletal health, osteocalcin has been recognized for its contributions to glucose metabolism and insulin sensitivity.
Osteocalcin is a potential modulator of systemic inflammation, as its levels are inversely related to those of pro-inflammatory cytokines, and it exhibits immunomodulatory properties. The dysregulation of osteocalcin in COVID-19 patients may influence metabolic health and inflammation during infection.
Sclerostin is another osteokine that negatively regulates bone formation by inhibiting the Wnt/β-catenin signaling pathway. Targeting sclerostin has been explored as a strategy for osteoporosis treatment. In COVID-19, the potential consequences of sclerostin modulation on bone health in infected patients, particularly those with prolonged bed rest and immobilization, are noteworthy.
The Interplay of Cardiokines in COVID-19
, a group of organokines secreted by the heart, have been increasingly recognized for their roles in cardiovascular health, metabolic regulation, and immune modulation. These molecules include atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and growth differentiation factor 15 (GDF-15).
ANP and BNP are traditionally associated with their natriuretic and blood pressure-regulating functions. However, they have pleiotropic effects on metabolic and inflammatory processes. In COVID-19 patients, elevated ANP and BNP levels are linked to myocardial injury and heart failure, common complications of severe disease.
GDF-15 is another cardiokine that has gained attention in the context of COVID-19. It is associated with inflammation, cell stress responses, and metabolic regulation. Elevated GDF-15 levels in COVID-19 patients are associated with poor clinical outcomes and may serve as a prognostic biomarker.
The intricate interplay of these cardiokines, combined with the viral infection's effects on the cardiovascular system, underscores the importance of understanding their roles in the pathophysiology of COVID-19.
Conclusion: Organokines as Emerging Players in COVID-19
The intricate relationships between organokines and COVID-19 open up a fascinating realm of research that may lead to innovative diagnostic and therapeutic strategies. The multifaceted roles of organokines in regulating metabolism, inflammation, and immune responses highlight their significance in disease pathophysiology and progression. These signaling molecules represent potential biomarkers for assessing the severity of COVID-19 and tailoring personalized treatment plans.
As researchers continue to unravel the complexities of organokines, their modulation and utilization in therapeutic interventions may hold the key to managing the viral infection more effectively. By delving deeper into the world of organokines, the scientific community can work toward improving patient outcomes and advancing our understanding of COVID-19, ultimately bringing us closer to overcoming this global health challenge.
The study findings were published in the peer reviewed journal: Cells.
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