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Nikhil Prasad  Fact checked by:Thailand Medical News Team Jan 31, 2024  3 weeks, 3 days, 16 hours, 43 minutes ago

COVID-19 News: SARS-CoV-2 Uses Receptors Like TLR-4, KIM-1/TIM-1 And CD147 To Cause Kidney Damage!

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COVID-19 News: SARS-CoV-2 Uses Receptors Like TLR-4, KIM-1/TIM-1 And CD147 To Cause Kidney Damage!
Nikhil Prasad  Fact checked by:Thailand Medical News Team Jan 31, 2024  3 weeks, 3 days, 16 hours, 43 minutes ago
COVID-19 News: The global battle against COVID-19 has revealed a multitude of challenges, with emerging evidence shedding light on the intricate ways in which the SARS-CoV-2 virus interacts with human cells. Among the myriad complications associated with COVID-19, kidney damage has emerged as a significant concern. This COVID-19 News report explores the latest findings from the American University of Beirut-Lebanon, University Paris Saclay, INSERM UMR_1180, France, Immeuble Les Gemeaux, France, and University of Mississippi Medical Center-USA, uncovering the involvement of toll-like receptor 4 (TLR-4), kidney injury molecule-1/T cell immunoglobulin mucin domain 1 (KIM-1/TIM-1), and cluster of differentiation 147 (CD147) in SARS-CoV-2-associated renal damage.

SARS-CoV-2 Uses Receptors Like TLR-4, KIM-1/TIM-1
And CD147 To Cause Kidney Damage

Thailand Medical News had previously reported that the SARS-CoV-2 virus is capable of using so many other receptors and not just ACE-2 receptors to gain entry into various host cells and where it causes a variety of specific medical or health issues for the human host.
The Alarming Complication: Kidney Damage in COVID-19
Notably, kidney damage in SARS-CoV-2 can manifest even in patients without pre-existing kidney disease. The incidence of acute kidney injury (AKI) has been reported to account for 5% in mild cases, escalating significantly in critically ill patients. Clinical studies have demonstrated that AKI is the most prominent extra-pulmonary complication in intensive care unit (ICU) patients, surpassing cardiac dysfunction and liver injury. Additionally, AKI prevalence in critically ill COVID-19 patients is significantly higher than in those with milder symptoms, becoming a strong predictor of 30-day mortality.
Histopathologic characteristics of SARS-CoV-2-related AKI include acute tubular necrosis and podocytopathy. The mechanisms involved encompass hemodynamic instability, renin–angiotensin aldosterone system disruption, direct invasion of kidney cells by the virus, and cytokine storms leading to inflammation and apoptosis. While angiotensin-converting enzyme 2 (ACE2) was initially considered the primary receptor, recent evidence points to toll-like receptor 4 (TLR4), kidney injury molecule-1/T cell immunoglobulin mucin domain 1 (KIM-1/TIM-1), and cluster of differentiation 147 (CD147) as alternative receptors for SARS-CoV-2, contributing to kidney injury.
SARS-CoV-2-Induced Kidney Abnormalities
Studies on autopsies of COVID-19 postmortem patients have reported SARS-CoV-2 antigen accumulation in renal epithelial tubules, podocytes , and proximal tubular epithelium. Microscopic examinations of ICU patients revealed glomerular, acute tubular, and tubulointerstitial injuries, emphasizing the complex nature of COVID-19-induced kidney abnormalities.
KIM-1/TIM-1 and TLR-4: Potential Culprits in Kidney Damage
Toll-like receptor 4 (TLR-4), expressed in renal proximal and distal tubular epithelial cells, has been implicated in the pathogenesis of kidney disease. Activation of TLR-4 exacerbates inflammation, stimulates adaptive immunity, and disrupts ion transport across tubules, contributing to tubular dysfunction. Recent evidence suggests TLR-4 binding to the SARS-CoV-2 spike protein as an alternative gateway, intensifying the hyperinflammatory response and potentially explaining thrombotic events observed in COVID-19 patients.
Kidney injury molecule-1 (KIM-1), also known as T cell immunoglobulin mucin domain 1 (TIM-1), is a receptor overexpressed in kidney injuries. KIM-1's dual role involves repairing tubular epithelial cells and promoting inflammation and fibrosis in chronic expression. The interaction between KIM-1 and SARS-CoV-2, evidenced by increased KIM-1 levels in severe COVID-19 cases, implicates it as a potential therapeutic target.
CD147: A Multifunctional Player in Kidney Damage
CD147, a transmembrane glycoprotein, is widely distributed in various organs, including the kidneys. Highly expressed in kidneys, CD147 is associated with inflammatory diseases and renal fibrosis. Recent research indicates CD147 as a potential entry route for SARS-CoV-2, localizing with the spike protein in infected cells. CD147's involvement in SARS-CoV-2-mediated renal damage makes it a promising therapeutic target.
Controversies and Future Directions
While evidence supports the involvement of TLR-4, KIM-1/TIM-1, and CD147 in SARS-CoV-2-associated kidney damage, controversies persist regarding the direct infection of kidney cells by the virus. Some studies suggest indirect mechanisms influenced by host responses, genetic factors, physiological disturbances, or therapies. Understanding the intricate relationship between SARS-CoV-2 and kidney damage remains a crucial area for future research.
Long-COVID and Chronic Kidney Disease: Unraveling the Connection
Recent research highlights a potential link between long-COVID and chronic kidney disease (CKD). Patients with pre-existing CKD face increased risks of severe COVID-19 infections, triggering multi-organ damage and an exaggerated inflammatory response. The mechanisms linking long-COVID to CKD involve direct renal damage, blood clot formation, and autonomic nervous system disruption. Furthermore, postural orthostatic tachycardia syndrome (POTS), a common long-COVID complication, may involve kidney-related factors.
The evolving landscape of COVID-19 research underscores the intricate interplay between SARS-CoV-2 and kidney damage. TLR-4, KIM-1/TIM-1, and CD147 emerge as potential therapeutic targets, offering avenues for drug development to mitigate the inflammatory response and enhance treatment efficacy. As the global scientific community delves deeper into understanding the complexities of SARS-CoV-2 and its impact on organs, ongoing research remains paramount to shaping effective therapeutic strategies and improving patient outcomes.
The study findings were published in the peer reviewed journal: Frontiers In Bioscience Landmark.
For the latest COVID-19 News, keep on logging to Thailand Medical News.
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